---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22295'
abstract:
- lang: eng
  text: 'Despite the functional diversity of over 100 causal genes1,2,3, phenotypic
    convergence across models may reveal common neurobiological processes in autism
    spectrum disorder (ASD). Here we profiled 251 samples from 11 monogenic mouse
    models of ASD using single-nucleus multi-omic sequencing across three developmental
    stages, both sexes and two brain regions. Despite genetic heterogeneity, ASD-linked
    mutations converged on perturbations of the radial glial cell lineage. These alterations
    reflect a transient developmental delay rather than lasting lineage misspecification
    and resolve by postnatal stages. Molecularly, the largest transcriptional differences
    emerged in neurons at early postnatal stages. These changes included downregulation
    of synaptic and ion channel-related genes, consistent with homeostatic adaptation
    or delayed maturation. Network analysis showed molecular convergence across models
    within each developmental stage, suggesting that diverse mutations linked to ASD
    impinge on common, stage-specific processes. Convergence becomes less pronounced
    by postnatal day 14, highlighting the dynamic nature of ASD-associated changes.
    Cross-genotype heterogeneity is superimposed on stage-specific effects. Electrophysiology
    corroborated this pattern: mutants generally showed altered neuronal excitability
    and synaptic properties with model-specific nuances. Our study also highlighted
    sex-specific gene expression alterations, with female mice often displaying larger
    effect sizes than male mice. Together, our findings provide a comprehensive view
    of developmental cellular and molecular dynamics across models of ASD.'
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank F. Freeman, V. Voronin and M. Ladron de Guevara for technical
  assistance; A. Stichelberger and S. Liegenfeld for the management of our animal
  colony; M. Schunn, C. Gold and the Preclinical Facility team for technical assistance;
  C. Jansen and the Scientific Computing Facility for bioinformatics support and technical
  assistance; the Biomedical Sequencing Facility at CeMM for assistance with next-generation
  sequencing; and J. Lin and T. Krausgruber in the laboratory of C. Bock for support
  with flow cytometry; J. Kirchner for illustrating the multi-omics approach depicted
  in Fig. 1; and all members of the laboratory of G.N. for their support and discussions.
  This study was supported by the Scientific Service Units of ISTA through resources
  provided by the Imaging & Optics Facility and the Laboratory Support Facility. Bulk
  RNA-seq was performed by the Next Generation Sequencing Facility at Vienna BioCenter
  Core Facilities, member of the Vienna BioCenter. This work was supported by a European
  Research Council Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02) and by
  the Austrian Science Fund (PE1028W1232 and PR1028FG1803) to G.N. Open access funding
  provided by Institute of Science and Technology (IST Austria).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lena A
  full_name: Schwarz, Lena A
  id: 29A8453C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Sergey
  full_name: Isaev, Sergey
  last_name: Isaev
- first_name: Michela
  full_name: Lisi, Michela
  id: 39383c1b-d3eb-11ef-8d6c-c8cdf4e10c8c
  last_name: Lisi
- first_name: Daniel
  full_name: Malzl, Daniel
  last_name: Malzl
- first_name: Christoph
  full_name: Büschl, Christoph
  id: 2a8c054c-0913-11ee-9159-f8ef515809ed
  last_name: Büschl
- first_name: Sabrina
  full_name: Ladstätter, Sabrina
  last_name: Ladstätter
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Matteo
  full_name: Barel, Matteo
  id: 8959927b-2236-11ed-bd6e-ea83d94ade0e
  last_name: Barel
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Chaitanya
  full_name: Chintaluri, Chaitanya
  id: BA06AFEE-A4BA-11EA-AE5C-14673DDC885E
  last_name: Chintaluri
  orcid: 0000-0003-4252-1608
- first_name: Sarah
  full_name: Gorkiewicz, Sarah
  id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
  last_name: Gorkiewicz
- first_name: Mohammad
  full_name: Goudarzi, Mohammad
  id: 3384113A-F248-11E8-B48F-1D18A9856A87
  last_name: Goudarzi
- first_name: Tereza
  full_name: Belinova, Tereza
  id: 0bf89b6a-d28b-11eb-8bd6-f43768e4d368
  last_name: Belinova
- first_name: Stephan
  full_name: Reichl, Stephan
  last_name: Reichl
- first_name: Gintarė
  full_name: Sendžikaitė, Gintarė
  id: dd6d52f2-c50d-11eb-9548-bcf0ff82b344
  last_name: Sendžikaitė
- first_name: Satish
  full_name: Arcot Jayaram, Satish
  id: b0bbee33-09f7-11eb-909c-8b358058d28a
  last_name: Arcot Jayaram
  orcid: 0000-0002-2479-2669
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Tim P
  full_name: Vogels, Tim P
  id: CB6FF8D2-008F-11EA-8E08-2637E6697425
  last_name: Vogels
  orcid: 0000-0003-3295-6181
- first_name: Jörg
  full_name: Menche, Jörg
  last_name: Menche
- first_name: Igor
  full_name: Adameyko, Igor
  last_name: Adameyko
- first_name: Peter Vasili
  full_name: Kharchenko, Peter Vasili
  id: 0095641e-7eb7-11f1-8665-aec51a2ab5e0
  last_name: Kharchenko
- first_name: Christoph
  full_name: Bock, Christoph
  last_name: Bock
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Schwarz LA, Dotter C, Isaev S, et al. Cortical development dynamics across
    autism spectrum disorder mouse models. <i>Nature</i>. 2026. doi:<a href="https://doi.org/10.1038/s41586-026-10679-1">10.1038/s41586-026-10679-1</a>
  apa: Schwarz, L. A., Dotter, C., Isaev, S., Lisi, M., Malzl, D., Büschl, C., … Novarino,
    G. (2026). Cortical development dynamics across autism spectrum disorder mouse
    models. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-026-10679-1">https://doi.org/10.1038/s41586-026-10679-1</a>
  chicago: Schwarz, Lena A, Christoph Dotter, Sergey Isaev, Michela Lisi, Daniel Malzl,
    Christoph Büschl, Sabrina Ladstätter, et al. “Cortical Development Dynamics across
    Autism Spectrum Disorder Mouse Models.” <i>Nature</i>. Springer Nature, 2026.
    <a href="https://doi.org/10.1038/s41586-026-10679-1">https://doi.org/10.1038/s41586-026-10679-1</a>.
  ieee: L. A. Schwarz <i>et al.</i>, “Cortical development dynamics across autism
    spectrum disorder mouse models,” <i>Nature</i>. Springer Nature, 2026.
  ista: Schwarz LA, Dotter C, Isaev S, Lisi M, Malzl D, Büschl C, Ladstätter S, Oliveira
    B, Barel M, Basilico B, Chintaluri C, Gorkiewicz S, Goudarzi M, Belinova T, Reichl
    S, Sendžikaitė G, Arcot Jayaram S, Koppensteiner P, Sommer CM, Vogels TP, Menche
    J, Adameyko I, Kharchenko PV, Bock C, Novarino G. 2026. Cortical development dynamics
    across autism spectrum disorder mouse models. Nature.
  mla: Schwarz, Lena A., et al. “Cortical Development Dynamics across Autism Spectrum
    Disorder Mouse Models.” <i>Nature</i>, Springer Nature, 2026, doi:<a href="https://doi.org/10.1038/s41586-026-10679-1">10.1038/s41586-026-10679-1</a>.
  short: L.A. Schwarz, C. Dotter, S. Isaev, M. Lisi, D. Malzl, C. Büschl, S. Ladstätter,
    B. Oliveira, M. Barel, B. Basilico, C. Chintaluri, S. Gorkiewicz, M. Goudarzi,
    T. Belinova, S. Reichl, G. Sendžikaitė, S. Arcot Jayaram, P. Koppensteiner, C.M.
    Sommer, T.P. Vogels, J. Menche, I. Adameyko, P.V. Kharchenko, C. Bock, G. Novarino,
    Nature (2026).
corr_author: '1'
dataavailabilitystatement: Single-nucleus multiomics data are available from the Gene
  Expression Omnibus (GSE328363). The mm10 reference genome was used for the alignment
  (refdata-cellranger-arc-mm10-2020-A-2.0.0, obtained from https://cf.10xgenomics.com/supp/cell-arc/refdata-cellranger-arc-mm10-2020-A-2.0.0.tar.gz).
  Single-cell data can be accessed and visualized through a CELLxGENE database (https://adameykolab.hifo.meduniwien.ac.at/cellxgene_public/filecrawl/.2026_Nature_Schwarz).
  Source data are provided with this paper. Scripts and analyses that support the
  main findings of this study are accessible in a GitHub repository (https://git.ista.ac.at/research-sofware/mouseome).
date_created: 2026-07-13T09:47:21Z
date_published: 2026-06-17T00:00:00Z
date_updated: 2026-08-04T09:29:55Z
day: '17'
ddc:
- '570'
department:
- _id: AnKi
- _id: GaNo
- _id: TiVo
- _id: ScienComp
- _id: GradSch
- _id: Bio
- _id: PreCl
doi: 10.1038/s41586-026-10679-1
external_id:
  pmid:
  - '42310454'
fulldoi: https://doi.org/10.1038/s41586-026-10679-1
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1038/s41586-026-10679-1
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  name: Toward an understanding of the brain interstitial system and the extracellular
    proteome in health and autism spectrum disorders
- _id: 9B91375C-BA93-11EA-9121-9846C619BF3A
  grant_number: '707964'
  name: Critical windows and reversibility of ASD associated with mutations in chromatin
    remodelers
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
- _id: ebb38b5d-77a9-11ec-83b8-a42e08120a88
  grant_number: FG1803 49015
  name: Neurobiology of anxiety in autism spectrum disorders
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/patterns-in-genetic-chaos/
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Cortical development dynamics across autism spectrum disorder mouse models
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2026'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '21746'
abstract:
- lang: eng
  text: As vertebrates transitioned from water to land, locomotion shifted from undulatory
    swimming to limb-based movement. How spinal circuits and their cell types evolved
    to support this transition remains unclear. We leverage frog metamorphosis, which
    recapitulates this transition within a single organism, to define how spinal circuits
    generate aquatic versus terrestrial motor patterns. At swim stages, spinal architecture
    is uniform, with a transcriptionally and anatomically homogeneous motor and interneurons.
    As limbs develop and their movement complexifies, spinal circuits expand in neuron
    number and subtype diversity. This expansion is most pronounced for V1 inhibitory
    neurons, which increase ∼70-fold and diversify into transcriptionally distinct
    subtypes. Disrupting transcription factors defining emerging motor and V1 populations
    reveals molecular segregation between swim and limb circuits, highlighting the
    role of subtype diversity in motor coordination. A multifold increase in inhibitory
    neuron diversity thus underlies the tail-to-limb locomotor transition, providing
    a framework for spinal circuit adaptation during vertebrate evolution.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: 'We would like to thank the members of the Sweeney Lab, Mario de
  Bono, Michael Forsthofer, Katharina Lust, and Meital Oren, for comments on the manuscript.
  We are also grateful to Tom Jessell and Chris Kintner for their scientific insight
  and mentorship during the conception of this project. It would also have not been
  possible without the technical support of the Aquatics and Imaging and Optics Facility
  support teams (ISTA). We thank Martin Estermann for preparing the initial draft
  of the graphical abstract and Niki Barolini for the final version. In addition,
  we thank our funding sources for providing the resources to do these experiments:
  GFF NÖ FTI Strategy Lower Austria dissertation grant FT121-D-046 (to D.V.), Horizon
  Europe ERC starting grant 101041551 (to Y.I., L.B.S., F.A.T., and D.V.), Special
  Research Program (SFB) of the Austrian Science Fund (FWF) project F7814-B (to L.B.S.),
  Austrian Science Fund (FWF) 10.55776/COE16 (to Y.I. and L.B.S.), NINDS 5R35NS116858
  (to J.S.D.), CZI grant DAF2020-225401 (DOI) 10.37921/120055ratwvi (to R.H.), NIH
  grant R01NS123116 (to J.B.B.), American Lebanese Syrian Associated Charities (ALSAC)
  (to J.B.B.), German Academic Exchange Service (DAAD) IFI grant 57515251-91853472
  (to Z.H.), and Project A.L.S. (to S.B.-M.).'
article_number: '117227'
article_processing_charge: Yes
article_type: original
author:
- first_name: David
  full_name: Vijatovic, David
  id: cf391e77-ec3c-11ea-a124-d69323410b58
  last_name: Vijatovic
  orcid: 0000-0002-5494-0941
- first_name: 'Florina Alexandra '
  full_name: 'Toma, Florina Alexandra '
  id: 2f73f876-f128-11eb-9611-b96b5a30cb0e
  last_name: Toma
- first_name: Y
  full_name: Ignatyev, Y
  last_name: Ignatyev
- first_name: Zoe P
  full_name: Harrington, Zoe P
  id: a8144562-32c9-11ee-b5ce-d9800628bda2
  last_name: Harrington
  orcid: 0009-0008-0158-4032
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Matthijs Geert
  full_name: Smits, Matthijs Geert
  id: 7a231d52-e216-11ee-a0bb-8acd55f8f1f0
  last_name: Smits
- first_name: Marco
  full_name: Dalla Vecchia, Marco
  id: 02a7a869-ff06-11ed-a87f-86649d6077e5
  last_name: Dalla Vecchia
- first_name: Alexandra J.
  full_name: Trevisan, Alexandra J.
  last_name: Trevisan
- first_name: Phillip
  full_name: Chapman, Phillip
  last_name: Chapman
- first_name: Mara
  full_name: Julseth, Mara
  id: 1cf464b2-dc7d-11ea-9b2f-f9b1aa9417d1
  last_name: Julseth
- first_name: Susan
  full_name: Brenner-Morton, Susan
  last_name: Brenner-Morton
- first_name: Mariano I.
  full_name: Gabitto, Mariano I.
  last_name: Gabitto
- first_name: Jeremy S.
  full_name: Dasen, Jeremy S.
  last_name: Dasen
- first_name: Jay B.
  full_name: Bikoff, Jay B.
  last_name: Bikoff
- first_name: Lora Beatrice Jaeger
  full_name: Sweeney, Lora Beatrice Jaeger
  id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
  last_name: Sweeney
  orcid: 0000-0001-9242-5601
citation:
  ama: Vijatovic D, Toma FA, Ignatyev Y, et al. Multifold increase in spinal inhibitory
    cell types with emergence of limb movement. <i>Cell Reports</i>. 2026;45(4). doi:<a
    href="https://doi.org/10.1016/j.celrep.2026.117227">10.1016/j.celrep.2026.117227</a>
  apa: Vijatovic, D., Toma, F. A., Ignatyev, Y., Harrington, Z. P., Sommer, C. M.,
    Hauschild, R., … Sweeney, L. B. (2026). Multifold increase in spinal inhibitory
    cell types with emergence of limb movement. <i>Cell Reports</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.celrep.2026.117227">https://doi.org/10.1016/j.celrep.2026.117227</a>
  chicago: Vijatovic, David, Florina Alexandra  Toma, Y Ignatyev, Zoe P Harrington,
    Christoph M Sommer, Robert Hauschild, Matthijs Geert Smits, et al. “Multifold
    Increase in Spinal Inhibitory Cell Types with Emergence of Limb Movement.” <i>Cell
    Reports</i>. Elsevier, 2026. <a href="https://doi.org/10.1016/j.celrep.2026.117227">https://doi.org/10.1016/j.celrep.2026.117227</a>.
  ieee: D. Vijatovic <i>et al.</i>, “Multifold increase in spinal inhibitory cell
    types with emergence of limb movement,” <i>Cell Reports</i>, vol. 45, no. 4. Elsevier,
    2026.
  ista: Vijatovic D, Toma FA, Ignatyev Y, Harrington ZP, Sommer CM, Hauschild R, Smits
    MG, Dalla Vecchia M, Trevisan AJ, Chapman P, Julseth M, Brenner-Morton S, Gabitto
    MI, Dasen JS, Bikoff JB, Sweeney LB. 2026. Multifold increase in spinal inhibitory
    cell types with emergence of limb movement. Cell Reports. 45(4), 117227.
  mla: Vijatovic, David, et al. “Multifold Increase in Spinal Inhibitory Cell Types
    with Emergence of Limb Movement.” <i>Cell Reports</i>, vol. 45, no. 4, 117227,
    Elsevier, 2026, doi:<a href="https://doi.org/10.1016/j.celrep.2026.117227">10.1016/j.celrep.2026.117227</a>.
  short: D. Vijatovic, F.A. Toma, Y. Ignatyev, Z.P. Harrington, C.M. Sommer, R. Hauschild,
    M.G. Smits, M. Dalla Vecchia, A.J. Trevisan, P. Chapman, M. Julseth, S. Brenner-Morton,
    M.I. Gabitto, J.S. Dasen, J.B. Bikoff, L.B. Sweeney, Cell Reports 45 (2026).
corr_author: '1'
date_created: 2026-04-19T22:07:43Z
date_published: 2026-04-28T00:00:00Z
date_updated: 2026-09-16T07:33:54Z
day: '28'
ddc:
- '570'
department:
- _id: LoSw
- _id: GradSch
- _id: TiVo
- _id: Bio
- _id: NiBa
doi: 10.1016/j.celrep.2026.117227
external_id:
  pmid:
  - '41964955 '
file:
- access_level: open_access
  checksum: 0d26cdb5b8d8dec3a911d8261a65cdef
  content_type: application/pdf
  creator: dernst
  date_created: 2026-05-04T12:20:10Z
  date_updated: 2026-05-04T12:20:10Z
  file_id: '21795'
  file_name: 2026_CellReports_Vijatovic.pdf
  file_size: 14925958
  relation: main_file
  success: 1
file_date_updated: 2026-05-04T12:20:10Z
fulldoi: https://doi.org/10.1016/j.celrep.2026.117227
has_accepted_license: '1'
intvolume: '        45'
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
  grant_number: '101041551'
  name: Development and Evolution of Tetrapod Motor Circuits
- _id: 8da85f50-16d5-11f0-9cad-eab8b0ff6c9e
  grant_number: F7814
  name: 'Stem Cell Modulation in Neural Development and Regeneration/ P14-Swim-to-limb
    transition: cell type to connection diversity'
- _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473
  grant_number: CZI01
  name: Tools for automation and feedback microscopy
- _id: bd73af52-d553-11ed-ba76-912049f0ac7a
  grant_number: FTI21-D-046
  name: Development of V1 interneuron diversity during swim-to-walk transition of
    Xenopus metamorphosis
- _id: cf428362-b037-11f1-b015-8277a8a2f63d
  grant_number: COE16
  name: Neuronal circuits in health and disease (Sweeney)
publication: Cell Reports
publication_identifier:
  eissn:
  - 2211-1247
  issn:
  - 2639-1856
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '22667'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Multifold increase in spinal inhibitory cell types with emergence of limb movement
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 45
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19003'
abstract:
- lang: eng
  text: 'Super-resolution methods provide far better spatial resolution than the optical
    diffraction limit of about half the wavelength of light (∼200-300 nm). Nevertheless,
    they have yet to attain widespread use in plants, largely due to plants’ challenging
    optical properties. Expansion microscopy improves effective resolution by isotropically
    increasing the physical distances between sample structures while preserving relative
    spatial arrangements and clearing the sample. However, its application to plants
    has been hindered by the rigid, mechanically cohesive structure of plant tissues.
    Here, we report on whole-mount expansion microscopy of thale cress (Arabidopsis
    thaliana) root tissues (PlantEx), achieving a four-fold resolution increase over
    conventional microscopy. Our results highlight the microtubule cytoskeleton organization
    and interaction between molecularly defined cellular constituents. Combining PlantEx
    with stimulated emission depletion (STED) microscopy, we increase nanoscale resolution
    and visualize the complex organization of subcellular organelles from intact tissues
    by example of the densely packed COPI-coated vesicles associated with the Golgi
    apparatus and put these into a cellular structural context. Our results show that
    expansion microscopy can be applied to increase effective imaging resolution in
    Arabidopsis root specimens. '
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: E-Lib
- _id: M-Shop
acknowledgement: "We gratefully acknowledge support by the Scientific Service Units
  at ISTA, including the Imaging and Optics and Lab Support facilities and the mechanical
  workshop and Library. We thank Philipp Velicky for STED microscope alignment.\r\nThis
  project has received funding from the European Research Council under the Horizon
  2020 Framework Programme (grant agreement No 742985, J.F.). It has also received
  funding from the Horizon 2020 Framework Programme under the Marie Skłodowska-Curie
  Grant Agreement No. 665385 (M.G.). S.T. has received funding as an ISTplus Fellow
  from the Horizon 2020 Framework Programme under Marie Skłodowska-Curie grant agreement
  no. 754411 and from EMBO via a Long-Term Fellowship (grant number ALTF 679-2018).
  M.R.T. received funding from the Austrian Academy of Sciences with DOC fellowship
  no. 26137. The project has further received funding from the Austrian Science Fund,
  via grant DK W1232 (M.R.T., N.A.D., and J.G.D). W.J. received a postdoctoral fellowship
  from the Human Frontier Science Program (LT000557/2018). The funders had no role
  in study design, data collection and analysis, decision to publish or preparation
  of the manuscript."
article_number: koaf006
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Michelle C
  full_name: Gallei, Michelle C
  id: 35A03822-F248-11E8-B48F-1D18A9856A87
  last_name: Gallei
  orcid: 0000-0003-1286-7368
- first_name: Sven M
  full_name: Truckenbrodt, Sven M
  id: 45812BD4-F248-11E8-B48F-1D18A9856A87
  last_name: Truckenbrodt
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Syamala
  full_name: Inumella, Syamala
  id: F8660870-D756-11E9-98C5-34DFE5697425
  last_name: Inumella
  orcid: 0009-0002-5890-120X
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Marek
  full_name: Randuch, Marek
  id: 6ac4636d-15b2-11ec-abd3-fb8df79972ae
  last_name: Randuch
- first_name: Alexander J
  full_name: Johnson, Alexander J
  id: 46A62C3A-F248-11E8-B48F-1D18A9856A87
  last_name: Johnson
  orcid: 0000-0002-2739-8843
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Gallei MC, Truckenbrodt SM, Kreuzinger C, et al. Super-resolution expansion
    microscopy in plant roots. <i>The Plant Cell</i>. 2025;37(4). doi:<a href="https://doi.org/10.1093/plcell/koaf006">10.1093/plcell/koaf006</a>
  apa: Gallei, M. C., Truckenbrodt, S. M., Kreuzinger, C., Inumella, S., Vistunou,
    V., Sommer, C. M., … Danzl, J. G. (2025). Super-resolution expansion microscopy
    in plant roots. <i>The Plant Cell</i>. Oxford University Press. <a href="https://doi.org/10.1093/plcell/koaf006">https://doi.org/10.1093/plcell/koaf006</a>
  chicago: Gallei, Michelle C, Sven M Truckenbrodt, Caroline Kreuzinger, Syamala Inumella,
    Vitali Vistunou, Christoph M Sommer, Mojtaba Tavakoli, et al. “Super-Resolution
    Expansion Microscopy in Plant Roots.” <i>The Plant Cell</i>. Oxford University
    Press, 2025. <a href="https://doi.org/10.1093/plcell/koaf006">https://doi.org/10.1093/plcell/koaf006</a>.
  ieee: M. C. Gallei <i>et al.</i>, “Super-resolution expansion microscopy in plant
    roots,” <i>The Plant Cell</i>, vol. 37, no. 4. Oxford University Press, 2025.
  ista: Gallei MC, Truckenbrodt SM, Kreuzinger C, Inumella S, Vistunou V, Sommer CM,
    Tavakoli M, Agudelo Duenas N, Vorlaufer J, Jahr W, Randuch M, Johnson AJ, Benková
    E, Friml J, Danzl JG. 2025. Super-resolution expansion microscopy in plant roots.
    The Plant Cell. 37(4), koaf006.
  mla: Gallei, Michelle C., et al. “Super-Resolution Expansion Microscopy in Plant
    Roots.” <i>The Plant Cell</i>, vol. 37, no. 4, koaf006, Oxford University Press,
    2025, doi:<a href="https://doi.org/10.1093/plcell/koaf006">10.1093/plcell/koaf006</a>.
  short: M.C. Gallei, S.M. Truckenbrodt, C. Kreuzinger, S. Inumella, V. Vistunou,
    C.M. Sommer, M. Tavakoli, N. Agudelo Duenas, J. Vorlaufer, W. Jahr, M. Randuch,
    A.J. Johnson, E. Benková, J. Friml, J.G. Danzl, The Plant Cell 37 (2025).
corr_author: '1'
date_created: 2025-02-05T06:52:06Z
date_published: 2025-04-01T00:00:00Z
date_updated: 2026-10-01T11:19:12Z
day: '01'
ddc:
- '580'
department:
- _id: EvBe
- _id: JoDa
- _id: JiFr
doi: 10.1093/plcell/koaf006
ec_funded: 1
external_id:
  isi:
  - '001462763100001'
  pmid:
  - '39792900'
file:
- access_level: open_access
  checksum: 9d3f8218ff37a29f29c48a7bbe831bd3
  content_type: application/pdf
  creator: dernst
  date_created: 2025-07-31T07:03:43Z
  date_updated: 2025-07-31T07:03:43Z
  file_id: '20092'
  file_name: 2025_PlantCell_Gallei.pdf
  file_size: 53904111
  relation: main_file
  success: 1
file_date_updated: 2025-07-31T07:03:43Z
fulldoi: https://doi.org/10.1093/plcell/koaf006
has_accepted_license: '1'
intvolume: '        37'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 269B5B22-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 679-2018
  name: UltraX - achieving sub-nanometer resolution in light microscopy using iterative
    X10 microscopy in combination with nanobodies and STED
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: The Plant Cell
publication_identifier:
  eissn:
  - 1532-298X
  issn:
  - 1040-4651
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
  record:
  - id: '18837'
    relation: research_data
    status: public
  - id: '18689'
    relation: earlier_version
    status: public
scopus_import: '1'
status: public
title: Super-resolution expansion microscopy in plant roots
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 37
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19704'
abstract:
- lang: eng
  text: The information-processing capability of the brain’s cellular network depends
    on the physical wiring pattern between neurons and their molecular and functional
    characteristics. Mapping neurons and resolving their individual synaptic connections
    can be achieved by volumetric imaging at nanoscale resolution1,2 with dense cellular
    labelling. Light microscopy is uniquely positioned to visualize specific molecules,
    but dense, synapse-level circuit reconstruction by light microscopy has been out
    of reach, owing to limitations in resolution, contrast and volumetric imaging
    capability. Here we describe light-microscopy-based connectomics (LICONN). We
    integrated specifically engineered hydrogel embedding and expansion with comprehensive
    deep-learning-based segmentation and analysis of connectivity, thereby directly
    incorporating molecular information into synapse-level reconstructions of brain
    tissue. LICONN will allow synapse-level phenotyping of brain tissue in biological
    experiments in a readily adoptable manner.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: ScienComp
- _id: PreCl
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank S. Dorkenwald and P. Li for critical reading of the manuscript,
  S. Loomba for discussions and E. Miguel for support with data handling. We acknowledge
  support from ISTA’s scientific service units: Imaging and Optics, Lab Support, Scientific
  Computing, the preclinical facility, the Miba Machine Shop and the library. We acknowledge
  funding from the following sources: Austrian Science Fund (FWF) grant DK W1232 (J.G.D.
  and M.R.T.); Austrian Academy of Sciences DOC fellowship 26137 (M.R.T.); Gesellschaft
  für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); the European Union’s
  Horizon 2020 research and innovation programme and Marie Skłodowska-Curie Actions
  Fellowship 665385 (J.L.); and the European Union’s Horizon 2020 research and innovation
  programme and European Research Council (ERC) grant 101044865 ‘SecretAutism’ (G.N.).Open
  access funding provided by Institute of Science and Technology (IST Austria).'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Michał
  full_name: Januszewski, Michał
  last_name: Januszewski
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Viren
  full_name: Jain, Viren
  last_name: Jain
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy-based connectomic
    reconstruction of mammalian brain tissue. <i>Nature</i>. 2025;642:398-410. doi:<a
    href="https://doi.org/10.1038/s41586-025-08985-1">10.1038/s41586-025-08985-1</a>
  apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas,
    N., Vorlaufer, J., … Danzl, J. G. (2025). Light-microscopy-based connectomic reconstruction
    of mammalian brain tissue. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-025-08985-1">https://doi.org/10.1038/s41586-025-08985-1</a>
  chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou,
    Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy-Based
    Connectomic Reconstruction of Mammalian Brain Tissue.” <i>Nature</i>. Springer
    Nature, 2025. <a href="https://doi.org/10.1038/s41586-025-08985-1">https://doi.org/10.1038/s41586-025-08985-1</a>.
  ieee: M. Tavakoli <i>et al.</i>, “Light-microscopy-based connectomic reconstruction
    of mammalian brain tissue,” <i>Nature</i>, vol. 642. Springer Nature, pp. 398–410,
    2025.
  ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer
    J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl
    JG. 2025. Light-microscopy-based connectomic reconstruction of mammalian brain
    tissue. Nature. 642, 398–410.
  mla: Tavakoli, Mojtaba, et al. “Light-Microscopy-Based Connectomic Reconstruction
    of Mammalian Brain Tissue.” <i>Nature</i>, vol. 642, Springer Nature, 2025, pp.
    398–410, doi:<a href="https://doi.org/10.1038/s41586-025-08985-1">10.1038/s41586-025-08985-1</a>.
  short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas,
    J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino,
    V. Jain, J.G. Danzl, Nature 642 (2025) 398–410.
corr_author: '1'
date_created: 2025-05-18T22:02:51Z
date_published: 2025-06-12T00:00:00Z
date_updated: 2026-10-02T09:59:44Z
day: '12'
ddc:
- '570'
department:
- _id: JoDa
- _id: GradSch
- _id: Bio
- _id: GaNo
doi: 10.1038/s41586-025-08985-1
ec_funded: 1
external_id:
  isi:
  - '001483477000001'
  pmid:
  - '40335689'
file:
- access_level: open_access
  checksum: ebc99d7108e728f46db0a009292675ef
  content_type: application/pdf
  creator: dernst
  date_created: 2025-07-03T06:55:20Z
  date_updated: 2025-07-03T06:55:20Z
  file_id: '19959'
  file_name: 2025_Nature_Tavakoli.pdf
  file_size: 133201290
  relation: main_file
  success: 1
file_date_updated: 2025-07-03T06:55:20Z
fulldoi: https://doi.org/10.1038/s41586-025-08985-1
has_accepted_license: '1'
intvolume: '       642'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 398-410
pmid: 1
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  name: Toward an understanding of the brain interstitial system and the extracellular
    proteome in health and autism spectrum disorders
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: Nature
publication_identifier:
  eissn:
  - 1476-4687
  issn:
  - 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA website
    relation: press_release
    url: https://ista.ac.at/en/news/piecing-together-the-brain-puzzle/
  record:
  - id: '18697'
    relation: research_data
    status: public
  - id: '18677'
    relation: earlier_version
    status: public
scopus_import: '1'
status: public
title: Light-microscopy-based connectomic reconstruction of mammalian brain tissue
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 642
year: '2025'
...
---
OA_place: repository
OA_type: green
_id: '19520'
abstract:
- lang: eng
  text: Vertebrates exhibit a wide range of motor behaviors, ranging from swimming
    to complex limb-based movements. Here we take advantage of frog metamorphosis,
    which captures a swim-to-limb-based movement transformation during the development
    of a single organism, to explore changes in the underlying spinal circuits. We
    find that the tadpole spinal cord contains small and largely homogeneous populations
    of motor neurons (MNs) and V1 interneurons (V1s) at early escape swimming stages.
    These neuronal populations only modestly increase in number and subtype heterogeneity
    with the emergence of free swimming. In contrast, during frog metamorphosis and
    the emergence of limb movement, there is a dramatic expansion of MN and V1 interneuron
    number and transcriptional heterogeneity, culminating in cohorts of neurons that
    exhibit striking molecular similarity to mammalian motor circuits. CRISPR/Cas9-mediated
    gene disruption of the limb MN and V1 determinants FoxP1 and Engrailed-1, respectively,
    results in severe but selective deficits in tail and limb function. Our work thus
    demonstrates that neural diversity scales exponentially with increasing behavioral
    complexity and illustrates striking evolutionary conservation in the molecular
    organization and function of motor circuits across species.
acknowledged_ssus:
- _id: Bio
acknowledgement: "We would like to thank the members of the Sweeney Lab (especially
  Stavros Papadopoulos and\r\nSophie Gobeil) for their contributions to this project
  and, in addition to the lab, Graziana Gatto\r\nand Mario de Bono, for discussion,
  and support. We are also grateful to Tom Jessell and Chris\r\nKintner for their
  scientific insight and mentorship during the conception of this project. This\r\nproject
  would also not have been possible with the technical support of the Matthias Nowak,\r\nVerena
  Mayer and the Aquatics as well as the Imaging and Optics Facility support teams\r\n(ISTA).
  In addition, we thank our funding sources for providing the resources to do these\r\nexperiments:
  FTI Strategy Lower Austria Dissertation Grant Number FT121-D-046 (D.V.);\r\nHorizon
  Europe ERC Starting Grant Number 101041551 (L.B.S., F.A.T. and D.V); Special\r\nResearch
  Program (SFB) of the Austrian Science Fund (FWF) Project number F7814-B (L.B.S);\r\nNINDS
  5R35NS116858 (J.S.D); CZI grant DAF2020-225401 (DOI): 10.37921/120055ratwvi\r\n(R.H.);
  NIH grant number R01NS123116 (J.B.B); American Lebanese Syrian Associated\r\nCharities
  (ALSAC) (J.B.B.); German Academic Exchange Service (DAAD) IFI Grant Number\r\n57515251-91853472
  (Z.H.); and Project A.L.S. (S.B-M.). "
article_processing_charge: No
author:
- first_name: David
  full_name: Vijatovic, David
  id: cf391e77-ec3c-11ea-a124-d69323410b58
  last_name: Vijatovic
- first_name: 'Florina Alexandra '
  full_name: 'Toma, Florina Alexandra '
  id: 2f73f876-f128-11eb-9611-b96b5a30cb0e
  last_name: Toma
- first_name: Zoe P
  full_name: Harrington, Zoe P
  id: a8144562-32c9-11ee-b5ce-d9800628bda2
  last_name: Harrington
  orcid: 0009-0008-0158-4032
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Alexandra J.
  full_name: Trevisan, Alexandra J.
  last_name: Trevisan
- first_name: Phillip
  full_name: Chapman, Phillip
  last_name: Chapman
- first_name: Mara
  full_name: Julseth, Mara
  id: 1cf464b2-dc7d-11ea-9b2f-f9b1aa9417d1
  last_name: Julseth
- first_name: Susan
  full_name: Brenner-Morton, Susan
  last_name: Brenner-Morton
- first_name: Mariano I.
  full_name: Gabitto, Mariano I.
  last_name: Gabitto
- first_name: Jeremy S.
  full_name: Dasen, Jeremy S.
  last_name: Dasen
- first_name: Jay B.
  full_name: Bikoff, Jay B.
  last_name: Bikoff
- first_name: Lora Beatrice Jaeger
  full_name: Sweeney, Lora Beatrice Jaeger
  id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
  last_name: Sweeney
  orcid: 0000-0001-9242-5601
citation:
  ama: Vijatovic D, Toma FA, Harrington ZP, et al. Spinal neuron diversity scales
    exponentially with swim-to-limb transformation during frog metamorphosis. <i>bioRxiv</i>.
    doi:<a href="https://doi.org/10.1101/2024.09.20.614050">10.1101/2024.09.20.614050</a>
  apa: Vijatovic, D., Toma, F. A., Harrington, Z. P., Sommer, C. M., Hauschild, R.,
    Trevisan, A. J., … Sweeney, L. B. (n.d.). Spinal neuron diversity scales exponentially
    with swim-to-limb transformation during frog metamorphosis. <i>bioRxiv</i>. <a
    href="https://doi.org/10.1101/2024.09.20.614050">https://doi.org/10.1101/2024.09.20.614050</a>
  chicago: Vijatovic, David, Florina Alexandra  Toma, Zoe P Harrington, Christoph
    M Sommer, Robert Hauschild, Alexandra J. Trevisan, Phillip Chapman, et al. “Spinal
    Neuron Diversity Scales Exponentially with Swim-to-Limb Transformation during
    Frog Metamorphosis.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2024.09.20.614050">https://doi.org/10.1101/2024.09.20.614050</a>.
  ieee: D. Vijatovic <i>et al.</i>, “Spinal neuron diversity scales exponentially
    with swim-to-limb transformation during frog metamorphosis,” <i>bioRxiv</i>. .
  ista: Vijatovic D, Toma FA, Harrington ZP, Sommer CM, Hauschild R, Trevisan AJ,
    Chapman P, Julseth M, Brenner-Morton S, Gabitto MI, Dasen JS, Bikoff JB, Sweeney
    LB. Spinal neuron diversity scales exponentially with swim-to-limb transformation
    during frog metamorphosis. bioRxiv, <a href="https://doi.org/10.1101/2024.09.20.614050">10.1101/2024.09.20.614050</a>.
  mla: Vijatovic, David, et al. “Spinal Neuron Diversity Scales Exponentially with
    Swim-to-Limb Transformation during Frog Metamorphosis.” <i>BioRxiv</i>, doi:<a
    href="https://doi.org/10.1101/2024.09.20.614050">10.1101/2024.09.20.614050</a>.
  short: D. Vijatovic, F.A. Toma, Z.P. Harrington, C.M. Sommer, R. Hauschild, A.J.
    Trevisan, P. Chapman, M. Julseth, S. Brenner-Morton, M.I. Gabitto, J.S. Dasen,
    J.B. Bikoff, L.B. Sweeney, BioRxiv (n.d.).
corr_author: '1'
date_created: 2025-04-07T08:48:28Z
date_published: 2024-09-27T00:00:00Z
date_updated: 2025-05-14T11:40:13Z
day: '27'
department:
- _id: LoSw
- _id: TiVo
- _id: Bio
- _id: NiBa
doi: 10.1101/2024.09.20.614050
fulldoi: https://doi.org/10.1101/2024.09.20.614050
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.09.20.614050
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: bd73af52-d553-11ed-ba76-912049f0ac7a
  grant_number: FTI21-D-046
  name: Development of V1 interneuron diversity during swim-to-walk transition of
    Xenopus metamorphosis
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
  grant_number: '101041551'
  name: Development and Evolution of Tetrapod Motor Circuits
- _id: c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473
  grant_number: CZI01
  name: Tools for automation and feedback microscopy
publication: bioRxiv
publication_status: submitted
status: public
title: Spinal neuron diversity scales exponentially with swim-to-limb transformation
  during frog metamorphosis
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '14257'
abstract:
- lang: eng
  text: Mapping the complex and dense arrangement of cells and their connectivity
    in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
    optical microscopy excels at visualizing specific molecules and individual cells
    but fails to provide tissue context. Here we developed Comprehensive Analysis
    of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
    from millimeter regional to nanometer synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS uses fixation-compatible
    extracellular labeling and optical imaging, including stimulated emission depletion
    or expansion microscopy, to comprehensively delineate cellular structures. It
    enables three-dimensional reconstruction of single synapses and mapping of synaptic
    connectivity by identification and analysis of putative synaptic cleft regions.
    Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
    and quantified the synaptic input and output structure of identified neurons.
    We furthermore demonstrate applicability to clinically derived human tissue samples,
    including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
    the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
  for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
  Erber for technical assistance; and M. Tomschik for support with obtaining human
  samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
  for computational support and hardware control. We are grateful to R. Shigemoto
  and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
  for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
  provided by S. Grant (University of Edinburgh). We acknowledge expert support by
  Institute of Science and Technology Austria’s scientific computing, imaging and
  optics, preclinical and lab support facilities and by the Miba machine shop and
  library. We gratefully acknowledge funding by the following sources: Austrian Science
  Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
  (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
  (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
  (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
  European Union’s Horizon 2020 research and innovation programme, European Research
  Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
  research and innovation programme, European Research Council (ERC) grant 692692
  – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
  the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
  Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Hana
  full_name: Korinkova, Hana
  id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
  last_name: Korinkova
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  full_name: Roessler, Karl
  last_name: Roessler
- first_name: Thomas
  full_name: Czech, Thomas
  last_name: Czech
- first_name: Romana
  full_name: Höftberger, Romana
  last_name: Höftberger
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
    across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2024;42:1051-1064.
    doi:<a href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>
  apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
    A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter
    to nanometer scales. <i>Nature Biotechnology</i>. Springer Nature. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>
  chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
    Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
    across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>. Springer
    Nature, 2024. <a href="https://doi.org/10.1038/s41587-023-01911-8">https://doi.org/10.1038/s41587-023-01911-8</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter
    to nanometer scales,” <i>Nature Biotechnology</i>, vol. 42. Springer Nature, pp.
    1051–1064, 2024.
  ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
    CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
    G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter
    to nanometer scales. Nature Biotechnology. 42, 1051–1064.
  mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
    to Nanometer Scales.” <i>Nature Biotechnology</i>, vol. 42, Springer Nature, 2024,
    pp. 1051–64, doi:<a href="https://doi.org/10.1038/s41587-023-01911-8">10.1038/s41587-023-01911-8</a>.
  short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
    C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
    Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.
corr_author: '1'
date_created: 2023-09-03T22:01:15Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-10-02T11:27:12Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
  isi:
  - '001065254200001'
  pmid:
  - '37653226'
file:
- access_level: open_access
  checksum: 57d5fafb16f02dcb9f7dddb1bd7e2a71
  content_type: application/pdf
  creator: dernst
  date_created: 2025-01-09T07:48:01Z
  date_updated: 2025-01-09T07:48:01Z
  file_id: '18784'
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  file_size: 26065165
  relation: main_file
  success: 1
file_date_updated: 2025-01-09T07:48:01Z
fulldoi: https://doi.org/10.1038/s41587-023-01911-8
has_accepted_license: '1'
intvolume: '        42'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1051-1064
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
  grant_number: LS18-022
  name: High content imaging to decode human immune cell interactions in health and
    allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
  eissn:
  - 1546-1696
  issn:
  - 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/danzllab/CATS
  record:
  - id: '18660'
    relation: dissertation_contains
    status: deleted
  - id: '13126'
    relation: research_data
    status: public
  - id: '18674'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Imaging brain tissue architecture across millimeter to nanometer scales
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 42
year: '2024'
...
---
OA_place: repository
_id: '18689'
abstract:
- lang: eng
  text: Multiplexed fluorescence microscopy imaging is widely used in biomedical applications.
    However, simultaneous imaging of multiple fluorophores can result in spectral
    leaks and overlapping, which greatly degrades image quality and subsequent analysis.
    Existing popular spectral unmixing methods are mainly based on computational intensive
    linear models and the performance is heavily dependent on the reference spectra,
    which may greatly preclude its further applications. In this paper, we propose
    a deep learning-based blindly spectral unmixing method, termed AutoUnmix, to imitate
    the physical spectral mixing process. A tranfer learning framework is further
    devised to allow our AutoUnmix adapting to a variety of imaging systems without
    retraining the network. Our proposed method has demonstrated real-time unmixing
    capabilities, surpassing existing methods by up to 100-fold in terms of unmixing
    speed. We further validate the reconstruction performance on both synthetic datasets
    and biological samples. The unmixing results of AutoUnmix achieve a highest SSIM
    of 0.99 in both three- and four-color imaging, with nearly up to 20% higher than
    other popular unmixing methods. Due to the desirable property of data independency
    and superior blind unmixing performance, we believe AutoUnmix is a powerful tool
    to study the interaction process of different organelles labeled by multiple fluorophores.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: "We gratefully acknowledge support by the Scientific Service Units
  at ISTA, including the Imaging and Optics and Lab Support facilities and the mechanical
  workshop and Library. We thank Philipp Velicky for STED microscope alignment.\r\n\r\nThis
  project has received funding from the Austrian Science Fund (FWF): I 3630-B25 (J.G.D)
  and the European Research Council (ERC) under the European Union’s Horizon 2020
  research and innovation programme (grant agreement No 742985, J.F.). It has also
  received funding from the European Union’s Horizon 2020 research and innovation
  programme under the Marie Skłodowska-Curie Grant Agreement No. 665385. S.T. has
  received funding as an ISTplus Fellow from the European Union’s Horizon 2020 Research
  and Innovation Programme under Marie Skłodowska-Curie grant agreement no. 754411
  and from an EMBO Long-Term Fellowship (grant number ALTF 679-2018). It has further
  received funding from the Austrian Science Fund (FWF) grant DK W1232 (M.T, N.A-D.,
  J.G.D). W.J. received funding via a Human Frontier Science Program postdoctoral
  fellowship LT000557/2018.\r\n\r\nThe funders had no role in study design, data collection
  and analysis, decision to publish or preparation of the manuscript."
article_processing_charge: No
author:
- first_name: Michelle C
  full_name: Gallei, Michelle C
  id: 35A03822-F248-11E8-B48F-1D18A9856A87
  last_name: Gallei
  orcid: 0000-0003-1286-7368
- first_name: Sven M
  full_name: Truckenbrodt, Sven M
  id: 45812BD4-F248-11E8-B48F-1D18A9856A87
  last_name: Truckenbrodt
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Syamala
  full_name: Inumella, Syamala
  id: F8660870-D756-11E9-98C5-34DFE5697425
  last_name: Inumella
  orcid: 0009-0002-5890-120X
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Marek
  full_name: Randuch, Marek
  id: 6ac4636d-15b2-11ec-abd3-fb8df79972ae
  last_name: Randuch
- first_name: Alexander J
  full_name: Johnson, Alexander J
  id: 46A62C3A-F248-11E8-B48F-1D18A9856A87
  last_name: Johnson
  orcid: 0000-0002-2739-8843
- first_name: Eva
  full_name: Benková, Eva
  id: 38F4F166-F248-11E8-B48F-1D18A9856A87
  last_name: Benková
  orcid: 0000-0002-8510-9739
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Gallei MC, Truckenbrodt SM, Kreuzinger C, et al. Super-resolution expansion
    microscopy in plant roots. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>
  apa: Gallei, M. C., Truckenbrodt, S. M., Kreuzinger, C., Inumella, S., Vistunou,
    V., Sommer, C. M., … Danzl, J. G. (n.d.). Super-resolution expansion microscopy
    in plant roots. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.02.21.581330">https://doi.org/10.1101/2024.02.21.581330</a>
  chicago: Gallei, Michelle C, Sven M Truckenbrodt, Caroline Kreuzinger, Syamala Inumella,
    Vitali Vistunou, Christoph M Sommer, Mojtaba Tavakoli, et al. “Super-Resolution
    Expansion Microscopy in Plant Roots.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2024.02.21.581330">https://doi.org/10.1101/2024.02.21.581330</a>.
  ieee: M. C. Gallei <i>et al.</i>, “Super-resolution expansion microscopy in plant
    roots,” <i>bioRxiv</i>. .
  ista: Gallei MC, Truckenbrodt SM, Kreuzinger C, Inumella S, Vistunou V, Sommer CM,
    Tavakoli M, Agudelo Duenas N, Vorlaufer J, Jahr W, Randuch M, Johnson AJ, Benková
    E, Friml J, Danzl JG. Super-resolution expansion microscopy in plant roots. bioRxiv,
    <a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>.
  mla: Gallei, Michelle C., et al. “Super-Resolution Expansion Microscopy in Plant
    Roots.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.02.21.581330">10.1101/2024.02.21.581330</a>.
  short: M.C. Gallei, S.M. Truckenbrodt, C. Kreuzinger, S. Inumella, V. Vistunou,
    C.M. Sommer, M. Tavakoli, N. Agudelo Duenas, J. Vorlaufer, W. Jahr, M. Randuch,
    A.J. Johnson, E. Benková, J. Friml, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '0'
date_created: 2024-12-19T12:28:00Z
date_published: 2024-02-21T00:00:00Z
date_updated: 2026-10-02T11:27:43Z
day: '21'
department:
- _id: EvBe
- _id: JoDa
- _id: JiFr
doi: 10.1101/2024.02.21.581330
ec_funded: 1
fulldoi: https://doi.org/10.1101/2024.02.21.581330
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.02.21.581330
month: '02'
oa: 1
oa_version: Preprint
project:
- _id: 261099A6-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742985'
  name: Tracing Evolution of Auxin Transport and Polarity in Plants
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
- _id: 269B5B22-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 679-2018
  name: UltraX - achieving sub-nanometer resolution in light microscopy using iterative
    X10 microscopy in combination with nanobodies and STED
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '19003'
    relation: later_version
    status: public
  - id: '18681'
    relation: dissertation_contains
    status: public
researchdata_availability: no
status: public
supplementarymaterial: no
title: Super-resolution expansion microscopy in plant roots
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: preprint
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
OA_place: repository
_id: '18677'
abstract:
- lang: eng
  text: The information-processing capability of the brain’s cellular network depends
    on the physical wiring pattern between neurons and their molecular and functional
    characteristics. Mapping neurons and resolving their individual synaptic connections
    can be achieved by volumetric imaging at nanoscale resolution with dense cellular
    labeling. Light microscopy is uniquely positioned to visualize specific molecules
    but dense, synapse-level circuit reconstruction by light microscopy has been out
    of reach due to limitations in resolution, contrast, and volumetric imaging capability.
    Here we developed light-microscopy based connectomics (LICONN). We integrated
    specifically engineered hydrogel embedding and expansion with comprehensive deep-learning
    based segmentation and analysis of connectivity, thus directly incorporating molecular
    information in synapse-level brain tissue reconstructions. LICONN will allow synapse-level
    brain tissue phenotyping in biological experiments in a readily adoptable manner.
acknowledged_ssus:
- _id: E-Lib
- _id: M-Shop
- _id: LifeSc
- _id: Bio
- _id: ScienComp
acknowledgement: "We thank Sven Dorkenwald and Peter Li for critical reading of the\r\nmanuscript.
  We acknowledge expert support by ISTA’s scientific service units: Imaging and\r\nOptics,
  Lab Support, Scientific Computing, Preclinical Facility, Miba Machine Shop, and
  Library.\r\nWe gratefully acknowledge funding by the following sources:\r\nAustrian
  Science Fund (FWF) grant DK W1232 (JGD, MRT)\r\nAustrian Academy of Sciences DOC
  fellowship 26137 (MRT)\r\nEU Horizon 2020 program, Marie Skłodowska-Curie Actions
  Fellowship 665385 (JL)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022
  (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European
  Research\r\nCouncil (ERC) grant 101044865 “SecretAutism.”\r\n"
article_processing_charge: No
author:
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Michał
  full_name: Januszewski, Michał
  last_name: Januszewski
- first_name: Vitali
  full_name: Vistunou, Vitali
  id: 7e146587-8972-11ed-ae7b-d7a32ea86a81
  last_name: Vistunou
- first_name: Nathalie
  full_name: Agudelo Duenas, Nathalie
  id: 40E7F008-F248-11E8-B48F-1D18A9856A87
  last_name: Agudelo Duenas
- first_name: Jakob
  full_name: Vorlaufer, Jakob
  id: 937696FA-C996-11E9-8C7C-CF13E6697425
  last_name: Vorlaufer
  orcid: 0009-0000-7590-3501
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Viren
  full_name: Jain, Viren
  last_name: Jain
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Tavakoli M, Lyudchik J, Januszewski M, et al. Light-microscopy based dense
    connectomic reconstruction of mammalian brain tissue. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>
  apa: Tavakoli, M., Lyudchik, J., Januszewski, M., Vistunou, V., Agudelo Duenas,
    N., Vorlaufer, J., … Danzl, J. G. (n.d.). Light-microscopy based dense connectomic
    reconstruction of mammalian brain tissue. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2024.03.01.582884">https://doi.org/10.1101/2024.03.01.582884</a>
  chicago: Tavakoli, Mojtaba, Julia Lyudchik, Michał Januszewski, Vitali Vistunou,
    Nathalie Agudelo Duenas, Jakob Vorlaufer, Christoph M Sommer, et al. “Light-Microscopy
    Based Dense Connectomic Reconstruction of Mammalian Brain Tissue.” <i>BioRxiv</i>,
    n.d. <a href="https://doi.org/10.1101/2024.03.01.582884">https://doi.org/10.1101/2024.03.01.582884</a>.
  ieee: M. Tavakoli <i>et al.</i>, “Light-microscopy based dense connectomic reconstruction
    of mammalian brain tissue,” <i>bioRxiv</i>. .
  ista: Tavakoli M, Lyudchik J, Januszewski M, Vistunou V, Agudelo Duenas N, Vorlaufer
    J, Sommer CM, Kreuzinger C, Oliveira B, Cenameri A, Novarino G, Jain V, Danzl
    JG. Light-microscopy based dense connectomic reconstruction of mammalian brain
    tissue. bioRxiv, <a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>.
  mla: Tavakoli, Mojtaba, et al. “Light-Microscopy Based Dense Connectomic Reconstruction
    of Mammalian Brain Tissue.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2024.03.01.582884">10.1101/2024.03.01.582884</a>.
  short: M. Tavakoli, J. Lyudchik, M. Januszewski, V. Vistunou, N. Agudelo Duenas,
    J. Vorlaufer, C.M. Sommer, C. Kreuzinger, B. Oliveira, A. Cenameri, G. Novarino,
    V. Jain, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '0'
date_created: 2024-12-18T14:48:24Z
date_published: 2024-07-08T00:00:00Z
date_updated: 2026-10-02T11:27:43Z
day: '08'
department:
- _id: GaNo
- _id: JoDa
doi: 10.1101/2024.03.01.582884
ec_funded: 1
fulldoi: https://doi.org/10.1101/2024.03.01.582884
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2024.03.01.582884
month: '07'
oa: 1
oa_version: Preprint
project:
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
  grant_number: '26137'
  name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
    Microscopy
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 34ba8964-11ca-11ed-8bc3-e15864e7e9a6
  grant_number: '101044865'
  name: Toward an understanding of the brain interstitial system and the extracellular
    proteome in health and autism spectrum disorders
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232-B24
  name: Molecular Drug Targets
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '19704'
    relation: later_version
    status: public
  - id: '18674'
    relation: dissertation_contains
    status: public
  - id: '18681'
    relation: dissertation_contains
    status: public
researchdata_availability: no
status: public
supplementarymaterial: no
title: Light-microscopy based dense connectomic reconstruction of mammalian brain
  tissue
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: preprint
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2024'
...
---
_id: '12830'
abstract:
- lang: eng
  text: Interstitial fluid (IF) accumulation between embryonic cells is thought to
    be important for embryo patterning and morphogenesis. Here, we identify a positive
    mechanical feedback loop between cell migration and IF relocalization and find
    that it promotes embryonic axis formation during zebrafish gastrulation. We show
    that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between
    the yolk cell and deep cell tissue to extend the embryonic axis, compress the
    overlying deep cell layer, thereby causing IF to flow from the deep cell layer
    to the boundary between the yolk cell and the deep cell layer, directly ahead
    of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion
    formation and migration by opening up the space into which the ppl moves and,
    thereby, the ability of the ppl to trigger IF relocalization by pushing against
    the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic
    feedback loop between cell migration and IF relocalization.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
acknowledgement: We thank Andrea Pauli (IMP) and Edouard Hannezo (ISTA) for fruitful
  discussions and support with the SPIM experiments; the Heisenberg group, and especially
  Feyza Nur Arslan and Alexandra Schauer, for discussions and feedback; Michaela Jović
  (ISTA) for help with the quantitative real-time PCR protocol; the bioimaging and
  zebrafish facilities of ISTA for continuous support; Stephan Preibisch (Janelia
  Research Campus) for support with the SPIM data analysis; and Nobuhiro Nakamura
  (Tokyo Institute of Technology) for sharing α1-Na+/K+-ATPase antibody. This work
  was supported by funding from the European Union (European Research Council Advanced
  grant 742573 to C.-P.H.), postdoctoral fellowships from EMBO (LTF-850-2017) and
  HFSP (LT000429/2018-L2) to D.P., and a PhD fellowship from the Studienstiftung des
  deutschen Volkes to F.P.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Karla
  full_name: Huljev, Karla
  id: 44C6F6A6-F248-11E8-B48F-1D18A9856A87
  last_name: Huljev
- first_name: Shayan
  full_name: Shamipour, Shayan
  id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
  last_name: Shamipour
- first_name: Diana C
  full_name: Nunes Pinheiro, Diana C
  id: 2E839F16-F248-11E8-B48F-1D18A9856A87
  last_name: Nunes Pinheiro
  orcid: 0000-0003-4333-7503
- first_name: Friedrich
  full_name: Preusser, Friedrich
  last_name: Preusser
- first_name: Irene
  full_name: Steccari, Irene
  id: 2705C766-9FE2-11EA-B224-C6773DDC885E
  last_name: Steccari
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Suyash
  full_name: Naik, Suyash
  id: 2C0B105C-F248-11E8-B48F-1D18A9856A87
  last_name: Naik
  orcid: 0000-0001-8421-5508
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
citation:
  ama: Huljev K, Shamipour S, Nunes Pinheiro DC, et al. A hydraulic feedback loop
    between mesendoderm cell migration and interstitial fluid relocalization promotes
    embryonic axis formation in zebrafish. <i>Developmental Cell</i>. 2023;58(7):582-596.e7.
    doi:<a href="https://doi.org/10.1016/j.devcel.2023.02.016">10.1016/j.devcel.2023.02.016</a>
  apa: Huljev, K., Shamipour, S., Nunes Pinheiro, D. C., Preusser, F., Steccari, I.,
    Sommer, C. M., … Heisenberg, C.-P. J. (2023). A hydraulic feedback loop between
    mesendoderm cell migration and interstitial fluid relocalization promotes embryonic
    axis formation in zebrafish. <i>Developmental Cell</i>. Elsevier. <a href="https://doi.org/10.1016/j.devcel.2023.02.016">https://doi.org/10.1016/j.devcel.2023.02.016</a>
  chicago: Huljev, Karla, Shayan Shamipour, Diana C Nunes Pinheiro, Friedrich Preusser,
    Irene Steccari, Christoph M Sommer, Suyash Naik, and Carl-Philipp J Heisenberg.
    “A Hydraulic Feedback Loop between Mesendoderm Cell Migration and Interstitial
    Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.” <i>Developmental
    Cell</i>. Elsevier, 2023. <a href="https://doi.org/10.1016/j.devcel.2023.02.016">https://doi.org/10.1016/j.devcel.2023.02.016</a>.
  ieee: K. Huljev <i>et al.</i>, “A hydraulic feedback loop between mesendoderm cell
    migration and interstitial fluid relocalization promotes embryonic axis formation
    in zebrafish,” <i>Developmental Cell</i>, vol. 58, no. 7. Elsevier, p. 582–596.e7,
    2023.
  ista: Huljev K, Shamipour S, Nunes Pinheiro DC, Preusser F, Steccari I, Sommer CM,
    Naik S, Heisenberg C-PJ. 2023. A hydraulic feedback loop between mesendoderm cell
    migration and interstitial fluid relocalization promotes embryonic axis formation
    in zebrafish. Developmental Cell. 58(7), 582–596.e7.
  mla: Huljev, Karla, et al. “A Hydraulic Feedback Loop between Mesendoderm Cell Migration
    and Interstitial Fluid Relocalization Promotes Embryonic Axis Formation in Zebrafish.”
    <i>Developmental Cell</i>, vol. 58, no. 7, Elsevier, 2023, p. 582–596.e7, doi:<a
    href="https://doi.org/10.1016/j.devcel.2023.02.016">10.1016/j.devcel.2023.02.016</a>.
  short: K. Huljev, S. Shamipour, D.C. Nunes Pinheiro, F. Preusser, I. Steccari, C.M.
    Sommer, S. Naik, C.-P.J. Heisenberg, Developmental Cell 58 (2023) 582–596.e7.
corr_author: '1'
date_created: 2023-04-16T22:01:07Z
date_published: 2023-04-10T00:00:00Z
date_updated: 2025-04-23T08:51:34Z
day: '10'
ddc:
- '570'
department:
- _id: CaHe
- _id: Bio
doi: 10.1016/j.devcel.2023.02.016
ec_funded: 1
external_id:
  isi:
  - '000982111800001'
  pmid:
  - '36931269'
file:
- access_level: open_access
  checksum: c80ca2ebc241232aacdb5aa4b4c80957
  content_type: application/pdf
  creator: dernst
  date_created: 2023-04-17T07:41:25Z
  date_updated: 2023-04-17T07:41:25Z
  file_id: '12842'
  file_name: 2023_DevelopmentalCell_Huljev.pdf
  file_size: 7925886
  relation: main_file
  success: 1
file_date_updated: 2023-04-17T07:41:25Z
fulldoi: https://doi.org/10.1016/j.devcel.2023.02.016
has_accepted_license: '1'
intvolume: '        58'
isi: 1
issue: '7'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 582-596.e7
pmid: 1
project:
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 850-2017
  name: Coordination of mesendoderm cell fate specification and internalization during
    zebrafish gastrulation
- _id: 266BC5CE-B435-11E9-9278-68D0E5697425
  grant_number: LT000429
  name: Coordination of mesendoderm fate specification and internalization during
    zebrafish gastrulation
publication: Developmental Cell
publication_identifier:
  eissn:
  - 1878-1551
  issn:
  - 1534-5807
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A hydraulic feedback loop between mesendoderm cell migration and interstitial
  fluid relocalization promotes embryonic axis formation in zebrafish
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 58
year: '2023'
...
---
OA_place: publisher
OA_type: hybrid
_id: '13267'
abstract:
- lang: eng
  text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual
    synapse level would create opportunities for decoding the dynamics and structure–function
    relationships of the brain’s complex and dense information processing network;
    however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise
    ratio and prohibitive light burden in optical imaging, whereas electron microscopy
    is inherently static. Here we solved these challenges by developing an integrated
    optical/machine-learning technology, LIONESS (live information-optimized nanoscopy
    enabling saturated segmentation). This leverages optical modifications to stimulated
    emission depletion microscopy in comprehensively, extracellularly labeled tissue
    and previous information on sample structure via machine learning to simultaneously
    achieve isotropic super-resolution, high signal-to-noise ratio and compatibility
    with living tissue. This allows dense deep-learning-based instance segmentation
    and 3D reconstruction at a synapse level, incorporating molecular, activity and
    morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
    (nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: E-Lib
- _id: LifeSc
- _id: M-Shop
acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance
  and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata
  for hardware control support and M. Cunha dos Santos for initial exploration of
  software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt,
  S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L.
  Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We
  acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and
  optics, preclinical, library and laboratory support facilities and by the Miba machine
  shop. We gratefully acknowledge funding by the following sources: Austrian Science
  Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.)
  and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung
  NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D.
  and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska
  Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research
  and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE
  (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.);
  and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research
  Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development
  grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship
  no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier
  Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science
  Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Eder
  full_name: Miguel Villalba, Eder
  id: 3FB91342-F248-11E8-B48F-1D18A9856A87
  last_name: Miguel Villalba
  orcid: 0000-0001-5665-0430
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Donglai
  full_name: Wei, Donglai
  last_name: Wei
- first_name: Zudi
  full_name: Lin, Zudi
  last_name: Lin
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Jakob
  full_name: Troidl, Jakob
  last_name: Troidl
- first_name: Johanna
  full_name: Beyer, Johanna
  last_name: Beyer
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Johannes
  full_name: Broichhagen, Johannes
  last_name: Broichhagen
- first_name: Seth G.N.
  full_name: Grant, Seth G.N.
  last_name: Grant
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Hanspeter
  full_name: Pfister, Hanspeter
  last_name: Pfister
- first_name: Bernd
  full_name: Bickel, Bernd
  id: 49876194-F248-11E8-B48F-1D18A9856A87
  last_name: Bickel
  orcid: 0000-0001-6511-9385
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction
    of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href="https://doi.org/10.1038/s41592-023-01936-6">10.1038/s41592-023-01936-6</a>
  apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D.,
    Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain
    tissue. <i>Nature Methods</i>. Springer Nature. <a href="https://doi.org/10.1038/s41592-023-01936-6">https://doi.org/10.1038/s41592-023-01936-6</a>
  chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik,
    Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction
    of Living Brain Tissue.” <i>Nature Methods</i>. Springer Nature, 2023. <a href="https://doi.org/10.1038/s41592-023-01936-6">https://doi.org/10.1038/s41592-023-01936-6</a>.
  ieee: P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain
    tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.
  ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson
    J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen
    J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense
    4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.
  mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain
    Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a
    href="https://doi.org/10.1038/s41592-023-01936-6">10.1038/s41592-023-01936-6</a>.
  short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin,
    J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri,
    J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel,
    J.G. Danzl, Nature Methods 20 (2023) 1256–1265.
corr_author: '1'
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2026-10-02T11:27:12Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
- _id: Bio
doi: 10.1038/s41592-023-01936-6
ec_funded: 1
external_id:
  isi:
  - '001025621500001'
  pmid:
  - '37429995'
file:
- access_level: open_access
  checksum: a68e845780a82ea36d0d4d3212a87c10
  content_type: application/pdf
  creator: dernst
  date_created: 2025-02-26T08:01:57Z
  date_updated: 2025-02-26T08:01:57Z
  file_id: '19088'
  file_name: 2023_NatureMethods_Velicky.pdf
  file_size: 14103039
  relation: main_file
  success: 1
file_date_updated: 2025-02-26T08:01:57Z
fulldoi: https://doi.org/10.1038/s41592-023-01936-6
has_accepted_license: '1'
intvolume: '        20'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 1256-1265
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
  grant_number: LS18-022
  name: High content imaging to decode human immune cell interactions in health and
    allergic disease
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 24F9549A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715767'
  name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and
    Modeling'
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
  call_identifier: H2020
  grant_number: '101026635'
  name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
  grant_number: LT00057
  name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Nature Methods
publication_identifier:
  eissn:
  - 1548-7105
  issn:
  - 1548-7091
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: software
    url: https://github.com/danzllab/LIONESS
  record:
  - id: '12817'
    relation: research_data
    status: public
  - id: '14770'
    relation: shorter_version
    status: public
  - id: '11943'
    relation: earlier_version
    status: public
  - id: '18674'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2023'
...
---
_id: '12239'
abstract:
- lang: eng
  text: Biological systems are the sum of their dynamic three-dimensional (3D) parts.
    Therefore, it is critical to study biological structures in 3D and at high resolution
    to gain insights into their physiological functions. Electron microscopy of metal
    replicas of unroofed cells and isolated organelles has been a key technique to
    visualize intracellular structures at nanometer resolution. However, many of these
    methods require specialized equipment and personnel to complete them. Here, we
    present novel accessible methods to analyze biological structures in unroofed
    cells and biochemically isolated organelles in 3D and at nanometer resolution,
    focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential
    trafficking organelles, their detailed structural information is lacking due to
    their poor preservation when observed via classical electron microscopy protocols
    experiments. First, we establish a method to visualize CCVs in unroofed cells
    using scanning transmission electron microscopy tomography, providing sufficient
    resolution to define the clathrin coat arrangements. Critically, the samples are
    prepared directly on electron microscopy grids, removing the requirement to use
    extremely corrosive acids, thereby enabling the use of this method in any electron
    microscopy lab. Secondly, we demonstrate that this standardized sample preparation
    allows the direct comparison of isolated CCV samples with those visualized in
    cells. Finally, to facilitate the high-throughput and robust screening of metal
    replicated samples, we provide a deep learning analysis method to screen the “pseudo
    3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes
    accessible ways to examine the 3D structure of biological samples and provide
    novel insights into the structure of plant CCVs.
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: Bio
acknowledgement: A.J. is supported by funding from the Austrian Science Fund I3630B25
  (to J.F.). This research was supported by the Scientific Service Units of Institute
  of Science and Technology Austria (ISTA) through resources provided by the Electron
  Microscopy Facility, Lab Support Facility, and the Imaging and Optics Facility.
  We acknowledge Prof. David Robinson (Heidelberg) and Prof. Jan Traas (Lyon) for
  making us aware of previously published classical on-grid preparation methods. No
  conflict of interest declared.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Alexander J
  full_name: Johnson, Alexander J
  id: 46A62C3A-F248-11E8-B48F-1D18A9856A87
  last_name: Johnson
  orcid: 0000-0002-2739-8843
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Tommaso
  full_name: Costanzo, Tommaso
  id: D93824F4-D9BA-11E9-BB12-F207E6697425
  last_name: Costanzo
  orcid: 0000-0001-9732-3815
- first_name: Dana A.
  full_name: Dahhan, Dana A.
  last_name: Dahhan
- first_name: Sebastian Y.
  full_name: Bednarek, Sebastian Y.
  last_name: Bednarek
- first_name: Jiří
  full_name: Friml, Jiří
  id: 4159519E-F248-11E8-B48F-1D18A9856A87
  last_name: Friml
  orcid: 0000-0002-8302-7596
citation:
  ama: Johnson AJ, Kaufmann W, Sommer CM, et al. Three-dimensional visualization of
    planta clathrin-coated vesicles at ultrastructural resolution. <i>Molecular Plant</i>.
    2022;15(10):1533-1542. doi:<a href="https://doi.org/10.1016/j.molp.2022.09.003">10.1016/j.molp.2022.09.003</a>
  apa: Johnson, A. J., Kaufmann, W., Sommer, C. M., Costanzo, T., Dahhan, D. A., Bednarek,
    S. Y., &#38; Friml, J. (2022). Three-dimensional visualization of planta clathrin-coated
    vesicles at ultrastructural resolution. <i>Molecular Plant</i>. Elsevier. <a href="https://doi.org/10.1016/j.molp.2022.09.003">https://doi.org/10.1016/j.molp.2022.09.003</a>
  chicago: Johnson, Alexander J, Walter Kaufmann, Christoph M Sommer, Tommaso Costanzo,
    Dana A. Dahhan, Sebastian Y. Bednarek, and Jiří Friml. “Three-Dimensional Visualization
    of Planta Clathrin-Coated Vesicles at Ultrastructural Resolution.” <i>Molecular
    Plant</i>. Elsevier, 2022. <a href="https://doi.org/10.1016/j.molp.2022.09.003">https://doi.org/10.1016/j.molp.2022.09.003</a>.
  ieee: A. J. Johnson <i>et al.</i>, “Three-dimensional visualization of planta clathrin-coated
    vesicles at ultrastructural resolution,” <i>Molecular Plant</i>, vol. 15, no.
    10. Elsevier, pp. 1533–1542, 2022.
  ista: Johnson AJ, Kaufmann W, Sommer CM, Costanzo T, Dahhan DA, Bednarek SY, Friml
    J. 2022. Three-dimensional visualization of planta clathrin-coated vesicles at
    ultrastructural resolution. Molecular Plant. 15(10), 1533–1542.
  mla: Johnson, Alexander J., et al. “Three-Dimensional Visualization of Planta Clathrin-Coated
    Vesicles at Ultrastructural Resolution.” <i>Molecular Plant</i>, vol. 15, no.
    10, Elsevier, 2022, pp. 1533–42, doi:<a href="https://doi.org/10.1016/j.molp.2022.09.003">10.1016/j.molp.2022.09.003</a>.
  short: A.J. Johnson, W. Kaufmann, C.M. Sommer, T. Costanzo, D.A. Dahhan, S.Y. Bednarek,
    J. Friml, Molecular Plant 15 (2022) 1533–1542.
corr_author: '1'
date_created: 2023-01-16T09:51:49Z
date_published: 2022-10-03T00:00:00Z
date_updated: 2025-04-15T07:32:09Z
day: '03'
ddc:
- '580'
department:
- _id: JiFr
- _id: EM-Fac
- _id: Bio
doi: 10.1016/j.molp.2022.09.003
external_id:
  isi:
  - '000882769800009'
  pmid:
  - '36081349'
file:
- access_level: open_access
  checksum: 04d5c12490052d03e4dc4412338a43dd
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-30T07:46:51Z
  date_updated: 2023-01-30T07:46:51Z
  file_id: '12435'
  file_name: 2022_MolecularPlant_Johnson.pdf
  file_size: 2307251
  relation: main_file
  success: 1
file_date_updated: 2023-01-30T07:46:51Z
fulldoi: https://doi.org/10.1016/j.molp.2022.09.003
has_accepted_license: '1'
intvolume: '        15'
isi: 1
issue: '10'
keyword:
- Plant Science
- Molecular Biology
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: 1533-1542
pmid: 1
project:
- _id: 26538374-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03630
  name: Molecular mechanisms of endocytic cargo recognition in plants
publication: Molecular Plant
publication_identifier:
  issn:
  - 1674-2052
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural
  resolution
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 15
year: '2022'
...
---
_id: '10791'
abstract:
- lang: eng
  text: The mammalian neocortex is composed of diverse neuronal and glial cell classes
    that broadly arrange in six distinct laminae. Cortical layers emerge during development
    and defects in the developmental programs that orchestrate cortical lamination
    are associated with neurodevelopmental diseases. The developmental principle of
    cortical layer formation depends on concerted radial projection neuron migration,
    from their birthplace to their final target position. Radial migration occurs
    in defined sequential steps, regulated by a large array of signaling pathways.
    However, based on genetic loss-of-function experiments, most studies have thus
    far focused on the role of cell-autonomous gene function. Yet, cortical neuron
    migration in situ is a complex process and migrating neurons traverse along diverse
    cellular compartments and environments. The role of tissue-wide properties and
    genetic state in radial neuron migration is however not clear. Here we utilized
    mosaic analysis with double markers (MADM) technology to either sparsely or globally
    delete gene function, followed by quantitative single-cell phenotyping. The MADM-based
    gene ablation paradigms in combination with computational modeling demonstrated
    that global tissue-wide effects predominate cell-autonomous gene function albeit
    in a gene-specific manner. Our results thus suggest that the genetic landscape
    in a tissue critically affects the overall migration phenotype of individual cortical
    projection neurons. In a broader context, our findings imply that global tissue-wide
    effects represent an essential component of the underlying etiology associated
    with focal malformations of cortical development in particular, and neurological
    diseases in general.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
- _id: Bio
acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
  Academy of Sciences. This work also received support from IST Austria institutional
  funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh
  Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC
  funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and
  C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical
  support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer
  lab for discussion. This research was supported by the Scientific Service Units
  of IST Austria through resources provided by the Imaging and Optics Facility, Lab
  Support Facility and Preclinical Facility."
article_number: kvac009
article_processing_charge: No
article_type: original
author:
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Michael
  full_name: Riedl, Michael
  id: 3BE60946-F248-11E8-B48F-1D18A9856A87
  last_name: Riedl
  orcid: 0000-0003-4844-6311
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Anna-Magdalena
  full_name: Heger, Anna-Magdalena
  id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
  last_name: Heger
- first_name: Susanne
  full_name: Laukoter, Susanne
  id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
  last_name: Laukoter
  orcid: 0000-0002-7903-3010
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Armel
  full_name: Nicolas, Armel
  id: 2A103192-F248-11E8-B48F-1D18A9856A87
  last_name: Nicolas
- first_name: Björn
  full_name: Hof, Björn
  id: 3A374330-F248-11E8-B48F-1D18A9856A87
  last_name: Hof
  orcid: 0000-0003-2057-2754
- first_name: Li Huei
  full_name: Tsai, Li Huei
  last_name: Tsai
- first_name: Thomas
  full_name: Rülicke, Thomas
  last_name: Rülicke
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic
    gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1).
    doi:<a href="https://doi.org/10.1093/oons/kvac009">10.1093/oons/kvac009</a>
  apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter,
    S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene
    function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford University
    Press. <a href="https://doi.org/10.1093/oons/kvac009">https://doi.org/10.1093/oons/kvac009</a>
  chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena
    Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override
    Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>.
    Oxford University Press, 2022. <a href="https://doi.org/10.1093/oons/kvac009">https://doi.org/10.1093/oons/kvac009</a>.
  ieee: A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene
    function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1,
    no. 1. Oxford University Press, 2022.
  ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM,
    Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects
    override cell-intrinsic gene function in radial neuron migration. Oxford Open
    Neuroscience. 1(1), kvac009.
  mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function
    in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009,
    Oxford University Press, 2022, doi:<a href="https://doi.org/10.1093/oons/kvac009">10.1093/oons/kvac009</a>.
  short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter,
    C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford
    Open Neuroscience 1 (2022).
corr_author: '1'
date_created: 2022-02-25T07:52:11Z
date_published: 2022-07-07T00:00:00Z
date_updated: 2026-04-07T13:29:13Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
- _id: BjHo
- _id: LifeSc
- _id: EM-Fac
doi: 10.1093/oons/kvac009
ec_funded: 1
external_id:
  pmid:
  - '38596707'
file:
- access_level: open_access
  checksum: 822e76e056c07099d1fb27d1ece5941b
  content_type: application/pdf
  creator: dernst
  date_created: 2023-08-16T08:00:30Z
  date_updated: 2023-08-16T08:00:30Z
  file_id: '14061'
  file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf
  file_size: 4846551
  relation: main_file
  success: 1
file_date_updated: 2023-08-16T08:00:30Z
fulldoi: https://doi.org/10.1093/oons/kvac009
has_accepted_license: '1'
intvolume: '         1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular mechanisms of radial neuronal migration
publication: Oxford Open Neuroscience
publication_identifier:
  eissn:
  - 2753-149X
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
  record:
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  - id: '14530'
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    status: public
status: public
title: Tissue-wide effects override cell-intrinsic gene function in radial neuron
  migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2022'
...
---
_id: '11160'
abstract:
- lang: eng
  text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
    cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
    macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
    affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
    we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
    with an accelerated and delayed generation of, respectively, inhibitory and excitatory
    neurons that yields, at days 60 and 120, symmetrically opposite expansions in
    their proportions. This imbalance is consistent with an enlargement of cerebral
    organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
    design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
    relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
    CHD8-dependent molecular defects related to an abnormal program of proliferation
    and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
    our study uncovers reproducible developmental alterations that may be employed
    for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
  supported by the Scientific Service Units (SSU) of IST Austria through resources
  provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
  work supported by the European Union’s Horizon 2020 research and innovation program
  (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
  the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
  and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
  were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
  full_name: Villa, Carlo Emanuele
  last_name: Villa
- first_name: Cristina
  full_name: Cheroni, Cristina
  last_name: Cheroni
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Alejandro
  full_name: López-Tóbon, Alejandro
  last_name: López-Tóbon
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Roberto
  full_name: Sacco, Roberto
  id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
  last_name: Sacco
- first_name: Aysan Çerağ
  full_name: Yahya, Aysan Çerağ
  id: 365A65F8-F248-11E8-B48F-1D18A9856A87
  last_name: Yahya
- first_name: Jasmin
  full_name: Morandell, Jasmin
  id: 4739D480-F248-11E8-B48F-1D18A9856A87
  last_name: Morandell
- first_name: Michele
  full_name: Gabriele, Michele
  last_name: Gabriele
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Mariano
  full_name: Gabitto, Mariano
  last_name: Gabitto
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- first_name: Giuseppe
  full_name: Testa, Giuseppe
  last_name: Testa
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
    to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>.
    2022;39(1). doi:<a href="https://doi.org/10.1016/j.celrep.2022.110615">10.1016/j.celrep.2022.110615</a>
  apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
    R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
    in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2022.110615">https://doi.org/10.1016/j.celrep.2022.110615</a>
  chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
    Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
    Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
    <i>Cell Reports</i>. Elsevier, 2022. <a href="https://doi.org/10.1016/j.celrep.2022.110615">https://doi.org/10.1016/j.celrep.2022.110615</a>.
  ieee: C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient
    alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol.
    39, no. 1. Elsevier, 2022.
  ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
    Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
    Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
    in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
  mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
    Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol.
    39, no. 1, 110615, Elsevier, 2022, doi:<a href="https://doi.org/10.1016/j.celrep.2022.110615">10.1016/j.celrep.2022.110615</a>.
  short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
    A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
    M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
corr_author: '1'
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2026-10-04T22:30:09Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
  isi:
  - '000785983900003'
  pmid:
  - '35385734'
file:
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  date_updated: 2022-04-15T09:06:25Z
  file_id: '11164'
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file_date_updated: 2022-04-15T09:06:25Z
fulldoi: https://doi.org/10.1016/j.celrep.2022.110615
has_accepted_license: '1'
intvolume: '        39'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I04205
  name: Identification of converging Molecular Pathways Across Chromatinopathies as
    Targets for Therapy
publication: Cell Reports
publication_identifier:
  issn:
  - 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
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  - id: '18681'
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    status: public
  - id: '12364'
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    status: public
scopus_import: '1'
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
  and inhibitory trajectories
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
---
_id: '11373'
abstract:
- lang: eng
  text: The actin-homologue FtsA is essential for E. coli cell division, as it links
    FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate
    cell constriction by switching from an inactive polymeric to an active monomeric
    conformation, which recruits downstream proteins and stabilizes the Z-ring. However,
    direct biochemical evidence for this mechanism is missing. Here, we use reconstitution
    experiments and quantitative fluorescence microscopy to study divisome activation
    in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive
    mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament
    stabilization and recruitment of FtsN. We could attribute these differences to
    a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using
    FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction.
    We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer
    that follows treadmilling filaments of FtsZ.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We acknowledge members of the Loose laboratory at IST Austria for
  helpful discussions—in particular L. Lindorfer for his assistance with cloning and
  purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing
  unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski
  (Lehigh University, Bethlehem, PA, USA) and S. Martin (University of Lausanne, Switzerland)
  for sharing their code for FRAP analysis. We are also thankful for the support by
  the Scientific Service Units (SSU) of IST Austria through resources provided by
  the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work
  was supported by the European Research Council through grant ERC 2015-StG-679239
  and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4
  to N.B. For the purpose of open access, we have applied a CC BY public copyright
  licence to any Author Accepted Manuscript version arising from this submission.
article_number: '2635'
article_processing_charge: No
article_type: original
author:
- first_name: Philipp
  full_name: Radler, Philipp
  id: 40136C2A-F248-11E8-B48F-1D18A9856A87
  last_name: Radler
  orcid: '0000-0001-9198-2182 '
- first_name: Natalia S.
  full_name: Baranova, Natalia S.
  id: 38661662-F248-11E8-B48F-1D18A9856A87
  last_name: Baranova
  orcid: 0000-0002-3086-9124
- first_name: Paulo R
  full_name: Dos Santos Caldas, Paulo R
  id: 38FCDB4C-F248-11E8-B48F-1D18A9856A87
  last_name: Dos Santos Caldas
  orcid: 0000-0001-6730-4461
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Maria D
  full_name: Lopez Pelegrin, Maria D
  id: 319AA9CE-F248-11E8-B48F-1D18A9856A87
  last_name: Lopez Pelegrin
- first_name: David
  full_name: Michalik, David
  id: B9577E20-AA38-11E9-AC9A-0930E6697425
  last_name: Michalik
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
citation:
  ama: Radler P, Baranova NS, Dos Santos Caldas PR, et al. In vitro reconstitution
    of Escherichia coli divisome activation. <i>Nature Communications</i>. 2022;13.
    doi:<a href="https://doi.org/10.1038/s41467-022-30301-y">10.1038/s41467-022-30301-y</a>
  apa: Radler, P., Baranova, N. S., Dos Santos Caldas, P. R., Sommer, C. M., Lopez
    Pelegrin, M. D., Michalik, D., &#38; Loose, M. (2022). In vitro reconstitution
    of Escherichia coli divisome activation. <i>Nature Communications</i>. Springer
    Nature. <a href="https://doi.org/10.1038/s41467-022-30301-y">https://doi.org/10.1038/s41467-022-30301-y</a>
  chicago: Radler, Philipp, Natalia S. Baranova, Paulo R Dos Santos Caldas, Christoph
    M Sommer, Maria D Lopez Pelegrin, David Michalik, and Martin Loose. “In Vitro
    Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>.
    Springer Nature, 2022. <a href="https://doi.org/10.1038/s41467-022-30301-y">https://doi.org/10.1038/s41467-022-30301-y</a>.
  ieee: P. Radler <i>et al.</i>, “In vitro reconstitution of Escherichia coli divisome
    activation,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.
  ista: Radler P, Baranova NS, Dos Santos Caldas PR, Sommer CM, Lopez Pelegrin MD,
    Michalik D, Loose M. 2022. In vitro reconstitution of Escherichia coli divisome
    activation. Nature Communications. 13, 2635.
  mla: Radler, Philipp, et al. “In Vitro Reconstitution of Escherichia Coli Divisome
    Activation.” <i>Nature Communications</i>, vol. 13, 2635, Springer Nature, 2022,
    doi:<a href="https://doi.org/10.1038/s41467-022-30301-y">10.1038/s41467-022-30301-y</a>.
  short: P. Radler, N.S. Baranova, P.R. Dos Santos Caldas, C.M. Sommer, M.D. Lopez
    Pelegrin, D. Michalik, M. Loose, Nature Communications 13 (2022).
corr_author: '1'
date_created: 2022-05-13T09:06:28Z
date_published: 2022-05-12T00:00:00Z
date_updated: 2026-10-04T22:30:10Z
day: '12'
ddc:
- '570'
department:
- _id: MaLo
doi: 10.1038/s41467-022-30301-y
ec_funded: 1
external_id:
  isi:
  - '000795171100037'
file:
- access_level: open_access
  checksum: 5af863ee1b95a0710f6ee864d68dc7a6
  content_type: application/pdf
  creator: dernst
  date_created: 2022-05-13T09:10:51Z
  date_updated: 2022-05-13T09:10:51Z
  file_id: '11374'
  file_name: 2022_NatureCommunications_Radler.pdf
  file_size: 6945191
  relation: main_file
  success: 1
file_date_updated: 2022-05-13T09:10:51Z
fulldoi: https://doi.org/10.1038/s41467-022-30301-y
has_accepted_license: '1'
intvolume: '        13'
isi: 1
keyword:
- General Physics and Astronomy
- General Biochemistry
- Genetics and Molecular Biology
- General Chemistry
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '679239'
  name: Self-Organization of the Bacterial Cell
- _id: fc38323b-9c52-11eb-aca3-ff8afb4a011d
  grant_number: P34607
  name: In vitro reconstitution of bacterial cell division
publication: Nature Communications
publication_identifier:
  issn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: erratum
    url: https://doi.org/10.1038/s41467-022-34485-1
  record:
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    relation: research_data
    status: public
  - id: '14280'
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    status: public
scopus_import: '1'
status: public
title: In vitro reconstitution of Escherichia coli divisome activation
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
OA_place: repository
_id: '11943'
abstract:
- lang: eng
  text: Complex wiring between neurons underlies the information-processing network
    enabling all brain functions, including cognition and memory. For understanding
    how the network is structured, processes information, and changes over time, comprehensive
    visualization of the architecture of living brain tissue with its cellular and
    molecular components would open up major opportunities. However, electron microscopy
    (EM) provides nanometre-scale resolution required for full <jats:italic>in-silico</jats:italic>
    reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and
    static representations. Light microscopy allows live observation, with super-resolution
    approaches<jats:sup>6–12</jats:sup> facilitating nanoscale visualization, but
    comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue
    photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise
    ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue.
    We developed an integrated imaging and analysis technology, adapting stimulated
    emission depletion (STED) microscopy<jats:sup>6,13</jats:sup> in extracellularly
    labelled tissue<jats:sup>14</jats:sup> for high SNR and near-isotropic resolution.
    Centrally, a two-stage deep-learning approach leveraged previously obtained information
    on sample structure to drastically reduce photo-burden and enable automated volumetric
    reconstruction down to single synapse level. Live reconstruction provides unbiased
    analysis of tissue architecture across time in relation to functional activity
    and targeted activation, and contextual understanding of molecular labelling.
    This adoptable technology will facilitate novel insights into the dynamic functional
    architecture of living brain tissue.
article_processing_charge: No
author:
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Eder
  full_name: Miguel Villalba, Eder
  id: 3FB91342-F248-11E8-B48F-1D18A9856A87
  last_name: Miguel Villalba
  orcid: 0000-0001-5665-0430
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Donglai
  full_name: Wei, Donglai
  last_name: Wei
- first_name: Zudi
  full_name: Lin, Zudi
  last_name: Lin
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Jakob
  full_name: Troidl, Jakob
  last_name: Troidl
- first_name: Johanna
  full_name: Beyer, Johanna
  last_name: Beyer
- first_name: Yoav
  full_name: Ben Simon, Yoav
  id: 43DF3136-F248-11E8-B48F-1D18A9856A87
  last_name: Ben Simon
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Wiebke
  full_name: Jahr, Wiebke
  id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
  last_name: Jahr
  orcid: 0000-0003-0201-2315
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Johannes
  full_name: Broichhagen, Johannes
  last_name: Broichhagen
- first_name: Seth G. N.
  full_name: Grant, Seth G. N.
  last_name: Grant
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Hanspeter
  full_name: Pfister, Hanspeter
  last_name: Pfister
- first_name: Bernd
  full_name: Bickel, Bernd
  id: 49876194-F248-11E8-B48F-1D18A9856A87
  last_name: Bickel
  orcid: 0000-0001-6511-9385
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction
    of living brain tissue. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2022.03.16.484431">10.1101/2022.03.16.484431</a>
  apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson,
    J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. <i>bioRxiv</i>.
    <a href="https://doi.org/10.1101/2022.03.16.484431">https://doi.org/10.1101/2022.03.16.484431</a>
  chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei,
    Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living
    Brain Tissue.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2022.03.16.484431">https://doi.org/10.1101/2022.03.16.484431</a>.
  ieee: P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,”
    <i>bioRxiv</i>. .
  ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl
    J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN,
    Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction
    of living brain tissue. bioRxiv, <a href="https://doi.org/10.1101/2022.03.16.484431">10.1101/2022.03.16.484431</a>.
  mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.”
    <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2022.03.16.484431">10.1101/2022.03.16.484431</a>.
  short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson,
    J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen,
    S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv
    (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2022-08-23T11:07:59Z
date_published: 2022-05-09T00:00:00Z
date_updated: 2026-10-04T22:31:02Z
day: '09'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
doi: 10.1101/2022.03.16.484431
fulldoi: https://doi.org/10.1101/2022.03.16.484431
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2022.03.16.484431
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '13267'
    relation: later_version
    status: public
  - id: '12470'
    relation: dissertation_contains
    status: public
status: public
title: Saturated reconstruction of living brain tissue
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
  text: Mapping the complex and dense arrangement of cells and their connectivity
    in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
    optical microscopy excels at visualizing specific molecules and individual cells
    but fails to provide tissue context. Here we developed Comprehensive Analysis
    of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
    from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
    brain preparations, including rodent and human. CATS leverages fixation-compatible
    extracellular labeling and advanced optical readout, in particular stimulated-emission
    depletion and expansion microscopy, to comprehensively delineate cellular structures.
    It enables 3D-reconstructing single synapses and mapping synaptic connectivity
    by identification and tailored analysis of putative synaptic cleft regions. Applying
    CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
    the system’s molecularly informed ultrastructure across spatial scales and assess
    local connectivity by reconstructing and quantifying the synaptic input and output
    structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
  full_name: Michalska, Julia M
  id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
  last_name: Michalska
  orcid: 0000-0003-3862-1235
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Philipp
  full_name: Velicky, Philipp
  id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
  last_name: Velicky
  orcid: 0000-0002-2340-7431
- first_name: Hana
  full_name: Korinkova, Hana
  id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
  last_name: Korinkova
- first_name: Jake
  full_name: Watson, Jake
  id: 63836096-4690-11EA-BD4E-32803DDC885E
  last_name: Watson
  orcid: 0000-0002-8698-3823
- first_name: Alban
  full_name: Cenameri, Alban
  id: 9ac8f577-2357-11eb-997a-e566c5550886
  last_name: Cenameri
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Alessandro
  full_name: Venturino, Alessandro
  id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
  last_name: Venturino
  orcid: 0000-0003-2356-9403
- first_name: Karl
  full_name: Roessler, Karl
  last_name: Roessler
- first_name: Thomas
  full_name: Czech, Thomas
  last_name: Czech
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
citation:
  ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
    across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>
  apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
    A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
    with super-resolution light microscopy. <i>bioRxiv</i>. <a href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>
  chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
    Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
    across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, n.d. <a
    href="https://doi.org/10.1101/2022.08.17.504272">https://doi.org/10.1101/2022.08.17.504272</a>.
  ieee: J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across
    scales with super-resolution light microscopy,” <i>bioRxiv</i>. .
  ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
    CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
    Uncovering brain tissue architecture across scales with super-resolution light
    microscopy. bioRxiv, <a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
    with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, doi:<a href="https://doi.org/10.1101/2022.08.17.504272">10.1101/2022.08.17.504272</a>.
  short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
    C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
    Jonas, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2026-10-04T22:31:02Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
fulldoi: https://doi.org/10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '12470'
    relation: dissertation_contains
    status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
  microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '10179'
abstract:
- lang: eng
  text: Inhibitory GABAergic interneurons migrate over long distances from their extracortical
    origin into the developing cortex. In humans, this process is uniquely slow and
    prolonged, and it is unclear whether guidance cues unique to humans govern the
    various phases of this complex developmental process. Here, we use fused cerebral
    organoids to identify key roles of neurotransmitter signaling pathways in guiding
    the migratory behavior of human cortical interneurons. We use scRNAseq to reveal
    expression of GABA, glutamate, glycine, and serotonin receptors along distinct
    maturation trajectories across interneuron migration. We develop an image analysis
    software package, TrackPal, to simultaneously assess 48 parameters for entire
    migration tracks of individual cells. By chemical screening, we show that different
    modes of interneuron migration depend on distinct neurotransmitter signaling pathways,
    linking transcriptional maturation of interneurons with their migratory behavior.
    Altogether, our study provides a comprehensive quantitative analysis of human
    interneuron migration and its functional modulation by neurotransmitter signaling.
acknowledgement: We thank all Knoblich laboratory members for continued support and
  discussions. We thank the IMP/IMBA BioOptics facility, particularly Pawel Pasierbek,
  Alberto Moreno Cencerrado and Gerald Schmauss, the IMP/IMBA Molecular Biology Service,
  in particular Robert Heinen, the IMP Bioinformatics facility, in particular Thomas
  Burkard, the Vienna Biocenter Core Facilities (VBCF) Histopathology facility, in
  particular Tamara Engelmaier, and the VBCF Next Generation Sequencing Facility,
  notably Volodymyr Shubchynskyy and Carmen Czepe. We would also like to thank Simon
  Haendeler for advice on statistical analyses, Jose Guzman for discussions and assistance
  with slice culture setups, Oliver L. Eichmueller for discussions and assistance
  with microscopy, and E.H. Gustafson, S. Wolfinger, and D. Reumann for technical
  assistance regarding generation of cerebral organoids. This project received funding
  from the European Union’s Horizon 2020 research and innovation program under the
  Marie Skłodowska-Curie fellowship agreement Nr.707109 awarded to J.A.B. Work in
  J.A.K.'s laboratory is supported by the Austrian Federal Ministry of Education,
  Science and Research, the Austrian Academy of Sciences, the City of Vienna, a Research
  Program of the Austrian Science Fund FWF (SFBF78 Stem Cell, F 7803-B) and a European
  Research Council (ERC) Advanced Grant under the European 20 Union’s Horizon 2020
  program (grant agreement no. 695642).
article_number: e108714
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Sunanjay
  full_name: Bajaj, Sunanjay
  last_name: Bajaj
- first_name: Joshua A.
  full_name: Bagley, Joshua A.
  last_name: Bagley
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Abel
  full_name: Vertesy, Abel
  last_name: Vertesy
- first_name: Sakurako
  full_name: Nagumo Wong, Sakurako
  last_name: Nagumo Wong
- first_name: Veronica
  full_name: Krenn, Veronica
  last_name: Krenn
- first_name: Julie
  full_name: Lévi-Strauss, Julie
  last_name: Lévi-Strauss
- first_name: Juergen A.
  full_name: Knoblich, Juergen A.
  last_name: Knoblich
citation:
  ama: Bajaj S, Bagley JA, Sommer CM, et al. Neurotransmitter signaling regulates
    distinct phases of multimodal human interneuron migration. <i>EMBO Journal</i>.
    2021;40(23). doi:<a href="https://doi.org/10.15252/embj.2021108714">10.15252/embj.2021108714</a>
  apa: Bajaj, S., Bagley, J. A., Sommer, C. M., Vertesy, A., Nagumo Wong, S., Krenn,
    V., … Knoblich, J. A. (2021). Neurotransmitter signaling regulates distinct phases
    of multimodal human interneuron migration. <i>EMBO Journal</i>. Embo Press. <a
    href="https://doi.org/10.15252/embj.2021108714">https://doi.org/10.15252/embj.2021108714</a>
  chicago: Bajaj, Sunanjay, Joshua A. Bagley, Christoph M Sommer, Abel Vertesy, Sakurako
    Nagumo Wong, Veronica Krenn, Julie Lévi-Strauss, and Juergen A. Knoblich. “Neurotransmitter
    Signaling Regulates Distinct Phases of Multimodal Human Interneuron Migration.”
    <i>EMBO Journal</i>. Embo Press, 2021. <a href="https://doi.org/10.15252/embj.2021108714">https://doi.org/10.15252/embj.2021108714</a>.
  ieee: S. Bajaj <i>et al.</i>, “Neurotransmitter signaling regulates distinct phases
    of multimodal human interneuron migration,” <i>EMBO Journal</i>, vol. 40, no.
    23. Embo Press, 2021.
  ista: Bajaj S, Bagley JA, Sommer CM, Vertesy A, Nagumo Wong S, Krenn V, Lévi-Strauss
    J, Knoblich JA. 2021. Neurotransmitter signaling regulates distinct phases of
    multimodal human interneuron migration. EMBO Journal. 40(23), e108714.
  mla: Bajaj, Sunanjay, et al. “Neurotransmitter Signaling Regulates Distinct Phases
    of Multimodal Human Interneuron Migration.” <i>EMBO Journal</i>, vol. 40, no.
    23, e108714, Embo Press, 2021, doi:<a href="https://doi.org/10.15252/embj.2021108714">10.15252/embj.2021108714</a>.
  short: S. Bajaj, J.A. Bagley, C.M. Sommer, A. Vertesy, S. Nagumo Wong, V. Krenn,
    J. Lévi-Strauss, J.A. Knoblich, EMBO Journal 40 (2021).
date_created: 2021-10-24T22:01:34Z
date_published: 2021-10-18T00:00:00Z
date_updated: 2023-08-14T08:05:23Z
day: '18'
ddc:
- '610'
department:
- _id: Bio
doi: 10.15252/embj.2021108714
external_id:
  isi:
  - '000708012800001'
  pmid:
  - '34661293'
file:
- access_level: open_access
  checksum: 78d2d02e775322297e774f72810a41a4
  content_type: application/pdf
  creator: alisjak
  date_created: 2021-12-13T14:54:14Z
  date_updated: 2021-12-13T14:54:14Z
  file_id: '10541'
  file_name: 2021_EMBO_Bajaj.pdf
  file_size: 7819881
  relation: main_file
  success: 1
file_date_updated: 2021-12-13T14:54:14Z
fulldoi: https://doi.org/10.15252/embj.2021108714
has_accepted_license: '1'
intvolume: '        40'
isi: 1
issue: '23'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: EMBO Journal
publication_identifier:
  eissn:
  - 1460-2075
  issn:
  - 0261-4189
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neurotransmitter signaling regulates distinct phases of multimodal human interneuron
  migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 40
year: '2021'
...
---
_id: '9429'
abstract:
- lang: eng
  text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
    lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
    leads to motor coordination deficits as well as ASD-relevant social and cognitive
    impairments. However, induction of Cul3 haploinsufficiency later in life does
    not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
    a critical developmental window. Here we show that Cul3 is essential to regulate
    neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
    display cortical lamination abnormalities. At the molecular level, we found that
    Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
    (Pls3), a previously unrecognized player of neural migration. Furthermore, we
    found that Pls3 cell-autonomously regulates cell migration by regulating actin
    cytoskeleton organization, and its levels are inversely proportional to neural
    migration speed. Finally, we provide evidence that cellular phenotypes associated
    with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
    of the intact allele in vitro, offering a proof of concept for a potential therapeutic
    approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
  Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
  management of our animal colony, as well as M. Schunn and the Preclinical Facility
  team for technical assistance. We thank K. Heesom and her team at the University
  of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
  and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
  lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
  and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
  fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
  2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
  the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
  (I3600-B27).
article_number: '3058'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
  full_name: Morandell, Jasmin
  id: 4739D480-F248-11E8-B48F-1D18A9856A87
  last_name: Morandell
- first_name: Lena A
  full_name: Schwarz, Lena A
  id: 29A8453C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Saren
  full_name: Tasciyan, Saren
  id: 4323B49C-F248-11E8-B48F-1D18A9856A87
  last_name: Tasciyan
  orcid: 0000-0003-1671-393X
- first_name: Georgi A
  full_name: Dimchev, Georgi A
  id: 38C393BE-F248-11E8-B48F-1D18A9856A87
  last_name: Dimchev
  orcid: 0000-0001-8370-6161
- first_name: Armel
  full_name: Nicolas, Armel
  id: 2A103192-F248-11E8-B48F-1D18A9856A87
  last_name: Nicolas
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Lisa
  full_name: Knaus, Lisa
  id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
  last_name: Knaus
- first_name: Zoe
  full_name: Dobler, Zoe
  id: D23090A2-9057-11EA-883A-A8396FC7A38F
  last_name: Dobler
- first_name: Emanuele
  full_name: Cacci, Emanuele
  last_name: Cacci
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
    homeostasis and cell migration during a critical window of brain development.
    <i>Nature Communications</i>. 2021;12(1). doi:<a href="https://doi.org/10.1038/s41467-021-23123-x">10.1038/s41467-021-23123-x</a>
  apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
    Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
    and cell migration during a critical window of brain development. <i>Nature Communications</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41467-021-23123-x">https://doi.org/10.1038/s41467-021-23123-x</a>
  chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
    Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
    Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
    <i>Nature Communications</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41467-021-23123-x">https://doi.org/10.1038/s41467-021-23123-x</a>.
  ieee: J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis
    and cell migration during a critical window of brain development,” <i>Nature Communications</i>,
    vol. 12, no. 1. Springer Nature, 2021.
  ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
    CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
    G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
    a critical window of brain development. Nature Communications. 12(1), 3058.
  mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
    and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>,
    vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href="https://doi.org/10.1038/s41467-021-23123-x">10.1038/s41467-021-23123-x</a>.
  short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
    C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
    J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
corr_author: '1'
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2026-10-04T22:30:15Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
  isi:
  - '000658769900010'
file:
- access_level: open_access
  checksum: 337e0f7959c35ec959984cacdcb472ba
  content_type: application/pdf
  creator: kschuh
  date_created: 2021-05-28T12:39:43Z
  date_updated: 2021-05-28T12:39:43Z
  file_id: '9430'
  file_name: 2021_NatureCommunications_Morandell.pdf
  file_size: 9358599
  relation: main_file
  success: 1
file_date_updated: 2021-05-28T12:39:43Z
fulldoi: https://doi.org/10.1038/s41467-021-23123-x
has_accepted_license: '1'
intvolume: '        12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
  grant_number: F7807
  name: Stem Cell Modulation in Neural Development and Regeneration/ P07-Neural stem
    cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
  eissn:
  - 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
  link:
  - relation: press_release
    url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
  record:
  - id: '19557'
    relation: dissertation_contains
    status: public
  - id: '7800'
    relation: earlier_version
    status: public
  - id: '12401'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
  critical window of brain development
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '7572'
abstract:
- lang: eng
  text: The polymerization–depolymerization dynamics of cytoskeletal proteins play
    essential roles in the self-organization of cytoskeletal structures, in eukaryotic
    as well as prokaryotic cells. While advances in fluorescence microscopy and in
    vitro reconstitution experiments have helped to study the dynamic properties of
    these complex systems, methods that allow to collect and analyze large quantitative
    datasets of the underlying polymer dynamics are still missing. Here, we present
    a novel image analysis workflow to study polymerization dynamics of active filaments
    in a nonbiased, highly automated manner. Using treadmilling filaments of the bacterial
    tubulin FtsZ as an example, we demonstrate that our method is able to specifically
    detect, track and analyze growth and shrinkage of polymers, even in dense networks
    of filaments. We believe that this automated method can facilitate the analysis
    of a large variety of dynamic cytoskeletal systems, using standard time-lapse
    movies obtained from experiments in vitro as well as in the living cell. Moreover,
    we provide scripts implementing this method as supplementary material.
alternative_title:
- Methods in Cell Biology
article_processing_charge: No
author:
- first_name: Paulo R
  full_name: Dos Santos Caldas, Paulo R
  id: 38FCDB4C-F248-11E8-B48F-1D18A9856A87
  last_name: Dos Santos Caldas
  orcid: 0000-0001-6730-4461
- first_name: Philipp
  full_name: Radler, Philipp
  id: 40136C2A-F248-11E8-B48F-1D18A9856A87
  last_name: Radler
  orcid: '0000-0001-9198-2182 '
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Martin
  full_name: Loose, Martin
  id: 462D4284-F248-11E8-B48F-1D18A9856A87
  last_name: Loose
  orcid: 0000-0001-7309-9724
citation:
  ama: 'Dos Santos Caldas PR, Radler P, Sommer CM, Loose M. Computational analysis
    of filament polymerization dynamics in cytoskeletal networks. In: Tran P, ed.
    <i>Methods in Cell Biology</i>. Vol 158. Elsevier; 2020:145-161. doi:<a href="https://doi.org/10.1016/bs.mcb.2020.01.006">10.1016/bs.mcb.2020.01.006</a>'
  apa: Dos Santos Caldas, P. R., Radler, P., Sommer, C. M., &#38; Loose, M. (2020).
    Computational analysis of filament polymerization dynamics in cytoskeletal networks.
    In P. Tran (Ed.), <i>Methods in Cell Biology</i> (Vol. 158, pp. 145–161). Elsevier.
    <a href="https://doi.org/10.1016/bs.mcb.2020.01.006">https://doi.org/10.1016/bs.mcb.2020.01.006</a>
  chicago: Dos Santos Caldas, Paulo R, Philipp Radler, Christoph M Sommer, and Martin
    Loose. “Computational Analysis of Filament Polymerization Dynamics in Cytoskeletal
    Networks.” In <i>Methods in Cell Biology</i>, edited by Phong  Tran, 158:145–61.
    Elsevier, 2020. <a href="https://doi.org/10.1016/bs.mcb.2020.01.006">https://doi.org/10.1016/bs.mcb.2020.01.006</a>.
  ieee: P. R. Dos Santos Caldas, P. Radler, C. M. Sommer, and M. Loose, “Computational
    analysis of filament polymerization dynamics in cytoskeletal networks,” in <i>Methods
    in Cell Biology</i>, vol. 158, P. Tran, Ed. Elsevier, 2020, pp. 145–161.
  ista: 'Dos Santos Caldas PR, Radler P, Sommer CM, Loose M. 2020.Computational analysis
    of filament polymerization dynamics in cytoskeletal networks. In: Methods in Cell
    Biology. Methods in Cell Biology, vol. 158, 145–161.'
  mla: Dos Santos Caldas, Paulo R., et al. “Computational Analysis of Filament Polymerization
    Dynamics in Cytoskeletal Networks.” <i>Methods in Cell Biology</i>, edited by
    Phong  Tran, vol. 158, Elsevier, 2020, pp. 145–61, doi:<a href="https://doi.org/10.1016/bs.mcb.2020.01.006">10.1016/bs.mcb.2020.01.006</a>.
  short: P.R. Dos Santos Caldas, P. Radler, C.M. Sommer, M. Loose, in:, P. Tran (Ed.),
    Methods in Cell Biology, Elsevier, 2020, pp. 145–161.
date_created: 2020-03-08T23:00:47Z
date_published: 2020-02-27T00:00:00Z
date_updated: 2026-04-08T07:26:30Z
day: '27'
department:
- _id: MaLo
doi: 10.1016/bs.mcb.2020.01.006
ec_funded: 1
editor:
- first_name: 'Phong '
  full_name: 'Tran, Phong '
  last_name: Tran
external_id:
  isi:
  - '000611826500008'
fulldoi: https://doi.org/10.1016/bs.mcb.2020.01.006
intvolume: '       158'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1101/839571
month: '02'
oa: 1
oa_version: Preprint
page: 145-161
project:
- _id: 2595697A-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '679239'
  name: Self-Organization of the Bacterial Cell
- _id: 260D98C8-B435-11E9-9278-68D0E5697425
  name: Reconstitution of Bacterial Cell Division Using Purified Components
publication: Methods in Cell Biology
publication_identifier:
  issn:
  - 0091-679X
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '8358'
    relation: part_of_dissertation
    status: public
scopus_import: '1'
status: public
title: Computational analysis of filament polymerization dynamics in cytoskeletal
  networks
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 158
year: '2020'
...
---
_id: '7800'
abstract:
- lang: eng
  text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
    (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models
    to evaluate the consequences of Cul3 mutations in vivo. Our results show that
    Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as
    ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical
    lamination abnormalities due to defective neuronal migration and reduced numbers
    of excitatory and inhibitory neurons. In line with the observed abnormal columnar
    organization, Cul3 haploinsufficiency is associated with decreased spontaneous
    excitatory and inhibitory activity in the cortex. At the molecular level, employing
    a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and
    adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal
    proteins in Cul3 mutant neuronal cells results in atypical organization of the
    actin mesh at the cell leading edge, likely causing the observed migration deficits.
    In contrast to these important functions early in development, Cul3 deficiency
    appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency
    in adult mice does not result in the behavioral defects observed in constitutive
    Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has
    a critical role in the regulation of cytoskeletal proteins and neuronal migration
    and that ASD-associated defects and behavioral abnormalities are primarily due
    to Cul3 functions at early developmental stages.
acknowledged_ssus:
- _id: PreCl
article_processing_charge: No
author:
- first_name: Jasmin
  full_name: Morandell, Jasmin
  id: 4739D480-F248-11E8-B48F-1D18A9856A87
  last_name: Morandell
- first_name: Lena A
  full_name: Schwarz, Lena A
  id: 29A8453C-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Bernadette
  full_name: Basilico, Bernadette
  id: 36035796-5ACA-11E9-A75E-7AF2E5697425
  last_name: Basilico
  orcid: 0000-0003-1843-3173
- first_name: Saren
  full_name: Tasciyan, Saren
  id: 4323B49C-F248-11E8-B48F-1D18A9856A87
  last_name: Tasciyan
  orcid: 0000-0003-1671-393X
- first_name: Armel
  full_name: Nicolas, Armel
  id: 2A103192-F248-11E8-B48F-1D18A9856A87
  last_name: Nicolas
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Caroline
  full_name: Kreuzinger, Caroline
  id: 382077BA-F248-11E8-B48F-1D18A9856A87
  last_name: Kreuzinger
- first_name: Lisa
  full_name: Knaus, Lisa
  id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
  last_name: Knaus
- first_name: Zoe
  full_name: Dobler, Zoe
  id: D23090A2-9057-11EA-883A-A8396FC7A38F
  last_name: Dobler
- first_name: Emanuele
  full_name: Cacci, Emanuele
  last_name: Cacci
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
    homeostasis and cell migration during a critical window of brain development.
    <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2020.01.10.902064 ">10.1101/2020.01.10.902064
    </a>
  apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer,
    C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis
    and cell migration during a critical window of brain development. <i>bioRxiv</i>.
    <a href="https://doi.org/10.1101/2020.01.10.902064 ">https://doi.org/10.1101/2020.01.10.902064
    </a>
  chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
    Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates
    Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of
    Brain Development.” <i>BioRxiv</i>, n.d. <a href="https://doi.org/10.1101/2020.01.10.902064
    ">https://doi.org/10.1101/2020.01.10.902064 </a>.
  ieee: J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis
    and cell migration during a critical window of brain development,” <i>bioRxiv</i>.
    .
  ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger
    C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton
    protein homeostasis and cell migration during a critical window of brain development.
    bioRxiv, <a href="https://doi.org/10.1101/2020.01.10.902064 ">10.1101/2020.01.10.902064
    </a>.
  mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
    and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>,
    doi:<a href="https://doi.org/10.1101/2020.01.10.902064 ">10.1101/2020.01.10.902064
    </a>.
  short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer,
    C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv
    (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2020-05-05T14:31:33Z
date_published: 2020-01-11T00:00:00Z
date_updated: 2026-10-04T22:31:09Z
day: '11'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
- _id: LifeSc
doi: '10.1101/2020.01.10.902064 '
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  file_size: 2931370
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file_date_updated: 2020-07-14T12:48:03Z
fulldoi: 'https://doi.org/10.1101/2020.01.10.902064 '
has_accepted_license: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Preprint
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I03600
  name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W1232
  name: Molecular Drug Targets
publication: bioRxiv
publication_status: draft
related_material:
  record:
  - id: '9429'
    relation: later_version
    status: public
  - id: '8620'
    relation: dissertation_contains
    status: public
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
  critical window of brain development
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
