---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21015'
abstract:
- lang: eng
text: Early embryo geometry is one of the most invariant species-specific traits,
yet its role in ensuring developmental reproducibility and robustness remains
underexplored. Here we show that in zebrafish, the geometry of the fertilized
egg—specifically its curvature and volume—serves as a critical initial condition
triggering a cascade of events that influence development. The embryo geometry
guides patterned asymmetric cell divisions in the blastoderm, generating radial
gradients of cell volume and nucleocytoplasmic ratio. These gradients generate
mitotic phase waves, with the nucleocytoplasmic ratio determining individual cell
cycle periods independently of other cells. We demonstrate that reducing cell
autonomy reshapes these waves, emphasizing the instructive role of geometry-derived
volume patterns in setting the intrinsic period of the cell cycle oscillator.
In addition to organizing cell cycles, early embryo geometry spatially patterns
zygotic genome activation at the midblastula transition, a key step in establishing
embryonic autonomy. Disrupting the embryo shape alters the zygotic genome activation
pattern and causes ectopic germ layer specification, underscoring the developmental
significance of geometry. Together, our findings reveal a symmetry-breaking function
of early embryo geometry in coordinating cell cycle and transcriptional patterning.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: ScienComp
- _id: LifeSc
acknowledgement: We thank N. Petridou (EMBL) for sharing results before publication.
N.M. was supported by funding from the European Union’s Horizon 2020 programme under
the Marie Skłodowska-Curie COFUND Actions ISTplus grant agreement number 754411.
Y.I.L. acknowledges funding from the European Union’s Horizon 2020 research and
innovation programme under the Marie Skłodowska-Curie grant agreement number 101034413.
The research was supported by funding to C.-P.H. from the NOMIS Foundation, Project
ID 1.844. We would like to thank past and present members of the Heisenberg and
Hannezo groups for discussions, particularly S. Shamipour, V. Doddihal, M. Jovic,
N. Hino, F. N. Arslan, R. Kobylinska and C. Camelo for feedback on the draft manuscript.
This research was supported by the Scientific Service Units (SSU) of Institute of
Science and Technology Austria through resources provided by the Aquatics Facility,
Imaging & Optics Facility (IOF), Scientific Computing (SciComp) facility and Lab
Support Facility (LSF). 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: Nikhil
full_name: Mishra, Nikhil
id: C4D70E82-1081-11EA-B3ED-9A4C3DDC885E
last_name: Mishra
orcid: 0000-0002-6425-5788
- first_name: Yuting I
full_name: Li, Yuting I
id: ee7a5ca8-8b71-11ed-b662-b3341c05b7eb
last_name: Li
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- 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: Mishra N, Li YI, Hannezo EB, Heisenberg C-PJ. Geometry-driven asymmetric cell
divisions pattern cell cycles and zygotic genome activation in the zebrafish embryo.
Nature Physics. 2026;22:139-150. doi:10.1038/s41567-025-03122-1
apa: Mishra, N., Li, Y. I., Hannezo, E. B., & Heisenberg, C.-P. J. (2026). Geometry-driven
asymmetric cell divisions pattern cell cycles and zygotic genome activation in
the zebrafish embryo. Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-025-03122-1
chicago: Mishra, Nikhil, Yuting I Li, Edouard B Hannezo, and Carl-Philipp J Heisenberg.
“Geometry-Driven Asymmetric Cell Divisions Pattern Cell Cycles and Zygotic Genome
Activation in the Zebrafish Embryo.” Nature Physics. Springer Nature, 2026.
https://doi.org/10.1038/s41567-025-03122-1.
ieee: N. Mishra, Y. I. Li, E. B. Hannezo, and C.-P. J. Heisenberg, “Geometry-driven
asymmetric cell divisions pattern cell cycles and zygotic genome activation in
the zebrafish embryo,” Nature Physics, vol. 22. Springer Nature, pp. 139–150,
2026.
ista: Mishra N, Li YI, Hannezo EB, Heisenberg C-PJ. 2026. Geometry-driven asymmetric
cell divisions pattern cell cycles and zygotic genome activation in the zebrafish
embryo. Nature Physics. 22, 139–150.
mla: Mishra, Nikhil, et al. “Geometry-Driven Asymmetric Cell Divisions Pattern Cell
Cycles and Zygotic Genome Activation in the Zebrafish Embryo.” Nature Physics,
vol. 22, Springer Nature, 2026, pp. 139–50, doi:10.1038/s41567-025-03122-1.
short: N. Mishra, Y.I. Li, E.B. Hannezo, C.-P.J. Heisenberg, Nature Physics 22 (2026)
139–150.
corr_author: '1'
date_created: 2026-01-20T10:12:19Z
date_published: 2026-01-05T00:00:00Z
date_updated: 2026-04-28T12:55:30Z
day: '05'
ddc:
- '570'
department:
- _id: EdHa
- _id: CaHe
doi: 10.1038/s41567-025-03122-1
ec_funded: 1
external_id:
oaworkid:
- W7118187193
file:
- access_level: open_access
checksum: 0ab7ac2fbcb61a364dba57152db64ed7
content_type: application/pdf
creator: dernst
date_created: 2026-01-21T08:21:11Z
date_updated: 2026-01-21T08:21:11Z
file_id: '21026'
file_name: 2026_NaturePhysics_Mishra.pdf
file_size: 7335694
relation: main_file
success: 1
file_date_updated: 2026-01-21T08:21:11Z
fulldoi: https://doi.org/10.1038/s41567-025-03122-1
has_accepted_license: '1'
intvolume: ' 22'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '01'
oa: 1
oa_version: Published Version
oaworkid: 1
page: 139-150
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
- _id: 917c023a-16d5-11f0-9cad-eb5cafc52090
name: Cytoplasmic self-organization into cell-like compartments as a common guiding
principle in early animal development
publication: Nature Physics
publication_identifier:
eissn:
- 1745-2481
issn:
- 1745-2473
issnl:
- ' 1745-2473'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: research_data
url: https://ista.ac.at/en/news/geometry-shapes-life/
scopus_import: '1'
status: public
title: Geometry-driven asymmetric cell divisions pattern cell cycles and zygotic genome
activation in the zebrafish embryo
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: 22
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21291'
abstract:
- lang: eng
text: The complexity and specificity of movement in vertebrates is driven by a rich
diversity of spinal motor and interneuron cell types. During development, eleven
spinal cord progenitor domains generate an equivalent number of cardinal neuron
types. How progenitor domains, individual progenitors, and post-mitotic diversity
relate is still unknown. We performed high-resolution, single-progenitor cell
lineage tracing in the embryonic mouse spinal cord using mosaic analysis with
double markers (MADM). Our quantitative study of lineage progression revealed
that spinal cord progenitors undergo highly variable numbers of proliferative,
neurogenic, and gliogenic cell divisions. The nascent clonally-related neurons
migrate radially over large distances, span the dorsoventral axis, and even cross
the midline, demonstrating striking bilaterality. Molecular and morphometric analysis
indicate high levels of progenitor multipotency, with an individual progenitor
capable of producing several molecularly and morphologically distinct neuron types,
as well as astrocytes. These findings redefine spinal cord development as a process
in which lineage variability — rather than rigid progenitor identity — drives
the generation of cellular diversity.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
acknowledgement: "We would like to thank Elizabeth Marin, Anna Kicheva, Igor Adameyko,
and James Briscoe as\r\nwell as members of the Sweeney and Hippemeyer labs and SFB
consortium for comments on\r\nthe manuscript. We are also grateful for the technical
support of the Preclinical and Imaging and\r\nOptics Facilities support teams (ISTA).
In addition, we thank our funding sources for providing\r\nthe resources to do these
experiments: Horizon Europe ERC Starting Grant Number 101041551\r\n(M.S.; L.B.S.);
Special Research Program (SFB) of the Austrian Science Fund (FWF)\r\nNeuroStem Modulation
Project numbers F7814-B (S.A.G.; M.S.; G.S.; and L.B.S.) and F7805\r\n(G.C. and
S.H.). S.A.G is supported by a Boehringer Ingelheim Fonds PhD Fellowship, F.D.S.N.\r\nby
an Institute of Science and Technology Austria (ISTA) GROW fellowship, and G.C.
by an\r\nISTA Plus postdoctoral fellowship from the European Commission. S.H./L.B.S.
and G.C. were\r\nadditionally supported by institutional funds from the ISTA and
the University of Exeter,\r\nrespectively. "
article_processing_charge: No
author:
- first_name: Sophie A
full_name: Gobeil, Sophie A
id: 2f3e9efb-eb24-11ec-86b2-88efb11d59fa
last_name: Gobeil
- first_name: Francisco
full_name: Da Silveira Neto, Francisco
id: 8cfb7412-10a7-11f1-add1-82b44e6418f2
last_name: Da Silveira Neto
- first_name: Giulia
full_name: Silvestrelli, Giulia
id: 12632ae8-799e-11ef-94a2-e5a3b5ef49e9
last_name: Silvestrelli
- first_name: Matthijs Geert
full_name: Smits, Matthijs Geert
id: 7a231d52-e216-11ee-a0bb-8acd55f8f1f0
last_name: Smits
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- 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: Gobeil SA, Da Silveira Neto F, Silvestrelli G, et al. Lineage origin of spinal
cord cell type diversity. bioRxiv. doi:10.64898/2026.02.12.705305
apa: Gobeil, S. A., Da Silveira Neto, F., Silvestrelli, G., Smits, M. G., Streicher,
C., Cheung, G. T., … Sweeney, L. B. (n.d.). Lineage origin of spinal cord cell
type diversity. bioRxiv. https://doi.org/10.64898/2026.02.12.705305
chicago: Gobeil, Sophie A, Francisco Da Silveira Neto, Giulia Silvestrelli, Matthijs
Geert Smits, Carmen Streicher, Giselle T Cheung, Simon Hippenmeyer, and Lora B.
Sweeney. “Lineage Origin of Spinal Cord Cell Type Diversity.” BioRxiv,
n.d. https://doi.org/10.64898/2026.02.12.705305.
ieee: S. A. Gobeil et al., “Lineage origin of spinal cord cell type diversity,”
bioRxiv. .
ista: Gobeil SA, Da Silveira Neto F, Silvestrelli G, Smits MG, Streicher C, Cheung
GT, Hippenmeyer S, Sweeney LB. Lineage origin of spinal cord cell type diversity.
bioRxiv, 10.64898/2026.02.12.705305.
mla: Gobeil, Sophie A., et al. “Lineage Origin of Spinal Cord Cell Type Diversity.”
BioRxiv, doi:10.64898/2026.02.12.705305.
short: S.A. Gobeil, F. Da Silveira Neto, G. Silvestrelli, M.G. Smits, C. Streicher,
G.T. Cheung, S. Hippenmeyer, L.B. Sweeney, BioRxiv (n.d.).
corr_author: '1'
date_created: 2026-02-17T11:36:20Z
date_published: 2026-02-16T00:00:00Z
date_updated: 2026-04-14T08:16:55Z
day: '16'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
doi: 10.64898/2026.02.12.705305
fulldoi: https://doi.org/10.64898/2026.02.12.705305
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.02.12.705305
month: '02'
oa: 1
oa_version: Preprint
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: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
publication: bioRxiv
publication_status: submitted
status: public
title: Lineage origin of spinal cord cell type diversity
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: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21848'
abstract:
- lang: eng
text: 'Despite the success of mRNA therapeutics, challenges remain in optimizing
immune responses and minimizing side effects. Cell-specific antigen delivery may
help reduce required doses and improve vaccine efficacy. In this study, we report
on a targeted delivery system for mRNA to a specific subset of skin-resident antigen-presenting
cells: Langerhans cells. By functionalizing lipid nanoparticles with a langerin-specific
glycomimetic ligand, we achieve selective mRNA delivery to both murine and human
primary Langerhans cells with minimal off-target uptake, at the same time resulting
in significantly increased mRNA translation. This targeted mRNA delivery not only
enhances antigen presentation and T-cell responses but also enables dose-sparing
and superior antitumor immunity compared with conventional immunization in a B16-OVA
tumor model. Importantly, our platform’s high compatibility with various lipid
nanoparticle formulations offers a flexible and precise tool for skin-directed
mRNA delivery.'
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank Mareike Rentzsch for her intellectual contributions during
the course of our discussions. We thank Michael Schunn from the Preclinical Facility
of the Institute of Science and Technology Austria for his continuous technical
support. Guarantor of the work is FS. This project was supported by “Seedfinancing”
(P2282679) of the Austrian Federal Ministry of Digital and Economic Affairs and
the Ministry of Climate Action and Energy, handled by the Austrian Wirtschaftsservice,
as well as by...
article_processing_charge: No
article_type: original
author:
- first_name: Klara
full_name: Klein, Klara
last_name: Klein
- first_name: Litty
full_name: Johnson, Litty
last_name: Johnson
- first_name: Ramona
full_name: Rîca, Ramona
last_name: Rîca
- first_name: Mirza
full_name: Sarcevic, Mirza
last_name: Sarcevic
- first_name: Gabriele
full_name: Carta, Gabriele
last_name: Carta
- first_name: Saskia
full_name: Seiser, Saskia
last_name: Seiser
- first_name: Adelheid
full_name: Elbe-Bürger, Adelheid
last_name: Elbe-Bürger
- first_name: Freyja
full_name: Langer, Freyja
id: 3C1BE782-F248-11E8-B48F-1D18A9856A87
last_name: Langer
- first_name: Nowras
full_name: Rahhal, Nowras
last_name: Rahhal
- first_name: Christoph
full_name: Rademacher, Christoph
last_name: Rademacher
- first_name: Robert
full_name: Wawrzinek, Robert
last_name: Wawrzinek
- first_name: Federica
full_name: Quattrone, Federica
last_name: Quattrone
- first_name: Florian
full_name: Sparber, Florian
last_name: Sparber
citation:
ama: 'Klein K, Johnson L, Rîca R, et al. Langerhans cell–targeted mRNA delivery:
A strategy for dose-sparing and enhanced antitumor immunity. Journal of Investigative
Dermatology. doi:10.1016/j.jid.2026.03.026'
apa: 'Klein, K., Johnson, L., Rîca, R., Sarcevic, M., Carta, G., Seiser, S., … Sparber,
F. (n.d.). Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing
and enhanced antitumor immunity. Journal of Investigative Dermatology.
Elsevier. https://doi.org/10.1016/j.jid.2026.03.026'
chicago: 'Klein, Klara, Litty Johnson, Ramona Rîca, Mirza Sarcevic, Gabriele Carta,
Saskia Seiser, Adelheid Elbe-Bürger, et al. “Langerhans Cell–Targeted MRNA Delivery:
A Strategy for Dose-Sparing and Enhanced Antitumor Immunity.” Journal of Investigative
Dermatology. Elsevier, n.d. https://doi.org/10.1016/j.jid.2026.03.026.'
ieee: 'K. Klein et al., “Langerhans cell–targeted mRNA delivery: A strategy
for dose-sparing and enhanced antitumor immunity,” Journal of Investigative
Dermatology. Elsevier.'
ista: 'Klein K, Johnson L, Rîca R, Sarcevic M, Carta G, Seiser S, Elbe-Bürger A,
Langer F, Rahhal N, Rademacher C, Wawrzinek R, Quattrone F, Sparber F. Langerhans
cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced antitumor
immunity. Journal of Investigative Dermatology.'
mla: 'Klein, Klara, et al. “Langerhans Cell–Targeted MRNA Delivery: A Strategy for
Dose-Sparing and Enhanced Antitumor Immunity.” Journal of Investigative Dermatology,
Elsevier, doi:10.1016/j.jid.2026.03.026.'
short: K. Klein, L. Johnson, R. Rîca, M. Sarcevic, G. Carta, S. Seiser, A. Elbe-Bürger,
F. Langer, N. Rahhal, C. Rademacher, R. Wawrzinek, F. Quattrone, F. Sparber, Journal
of Investigative Dermatology (n.d.).
date_created: 2026-05-10T22:02:16Z
date_published: 2026-04-07T00:00:00Z
date_updated: 2026-05-11T06:07:32Z
day: '07'
department:
- _id: PreCl
doi: 10.1016/j.jid.2026.03.026
fulldoi: https://doi.org/10.1016/j.jid.2026.03.026
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2025.06.25.661517
month: '04'
oa: 1
oa_version: Preprint
publication: Journal of Investigative Dermatology
publication_identifier:
eissn:
- 1523-1747
issn:
- 0022-202X
publication_status: inpress
publisher: Elsevier
scopus_import: '1'
status: public
title: 'Langerhans cell–targeted mRNA delivery: A strategy for dose-sparing and enhanced
antitumor immunity'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21962'
abstract:
- lang: eng
text: The generation of faithful cell-type diversity and correct projection neuron
numbers is essential for cerebral cortex development. Corticogenesis is however
susceptible to genetic interference of critical signaling pathways, including
mutations in Mtor/Rptor that lead to microcephaly. How the loss of Rptor/mTORC1
function affects cortical developmental programs, at single cell level, is still
unknown. Here, we utilized Mosaic Analysis with Double Markers (MADM) technology
to probe Rptor gene function upon sparse single cell- or global tissue-wide ablation.
We found that tissue-wide effects drive the etiology of cortical microcephaly
upon loss of Rptor, rather than deficits in projection neuron genesis. Conversely,
Rptor function is cell-autonomously required for postnatal projection neuron survival
in a highly cell-type-specific manner. Collectively, our results suggest that
the fine balance of precise cell-type-specific cell-autonomous Rptor/mTORC1 function
in concert with non-cell-autonomous tissue-wide effects is essential for the development
of a properly-sized cerebral cortex with accurate projection neuron diversity.
acknowledged_ssus:
- _id: PreCl
- _id: LifeSc
- _id: MassSpec
- _id: Bio
acknowledgement: "We thank A. Heger (IST Austria Preclinical Facility), A. Sommer
(VBCF GmbH, NGS Unit), and A.\r\nNicolas (IST Austria Lab Support Facility / Mass
Spectrometry Facility) for technical support; K. Ferencak,\r\nI. Aykara, P. Hirschfeld,
E. Fisher, S. Laukoter, L. Andersen for initial experiments and/or assistance; and\r\nall
members of the Hippenmeyer lab for discussion. This research was supported by the
Scientific Service\r\nUnits (SSU) of IST Austria through resources provided by the
Imaging and Optics- (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF).
R.B. received support from FWF Meitner-Programm (M 2416). This\r\nwork was also
supported by IST Austria institutional funds; the People Programme (Marie Curie
Actions)\r\nof the European Union’s Seventh Framework Programme (FP7/2007-2013)
under REA grant agreement\r\nNo 618444 to S.H., and the European Research Council
(ERC) under the European Union’s Horizon 2020\r\nresearch and innovation programme
(grant agreement No 725780 LinPro) to S.H."
article_processing_charge: No
author:
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Thomas
full_name: Krausgruber, Thomas
last_name: Krausgruber
- first_name: Martin
full_name: Senekowitsch, Martin
last_name: Senekowitsch
- first_name: Matthias
full_name: Farlik, Matthias
last_name: Farlik
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- 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: Villalba Requena A, Beattie RJ, Pauler F, et al. Mtor/Rptor function globally
prevents cortical microcephaly and cell-autonomously promotes postnatal neuron
survival in cell type specific manner. bioRxiv. doi:10.64898/2026.05.01.722172
apa: Villalba Requena, A., Beattie, R. J., Pauler, F., Streicher, C., Miranda, O.,
Krausgruber, T., … Hippenmeyer, S. (n.d.). Mtor/Rptor function globally prevents
cortical microcephaly and cell-autonomously promotes postnatal neuron survival
in cell type specific manner. bioRxiv. https://doi.org/10.64898/2026.05.01.722172
chicago: Villalba Requena, Ana, Robert J Beattie, Florian Pauler, Carmen Streicher,
Osvaldo Miranda, Thomas Krausgruber, Martin Senekowitsch, et al. “Mtor/Rptor Function
Globally Prevents Cortical Microcephaly and Cell-Autonomously Promotes Postnatal
Neuron Survival in Cell Type Specific Manner.” BioRxiv, n.d. https://doi.org/10.64898/2026.05.01.722172.
ieee: A. Villalba Requena et al., “Mtor/Rptor function globally prevents
cortical microcephaly and cell-autonomously promotes postnatal neuron survival
in cell type specific manner,” bioRxiv. .
ista: Villalba Requena A, Beattie RJ, Pauler F, Streicher C, Miranda O, Krausgruber
T, Senekowitsch M, Farlik M, Bock C, Rülicke T, Hippenmeyer S. Mtor/Rptor function
globally prevents cortical microcephaly and cell-autonomously promotes postnatal
neuron survival in cell type specific manner. bioRxiv, 10.64898/2026.05.01.722172.
mla: Villalba Requena, Ana, et al. “Mtor/Rptor Function Globally Prevents Cortical
Microcephaly and Cell-Autonomously Promotes Postnatal Neuron Survival in Cell
Type Specific Manner.” BioRxiv, doi:10.64898/2026.05.01.722172.
short: A. Villalba Requena, R.J. Beattie, F. Pauler, C. Streicher, O. Miranda, T.
Krausgruber, M. Senekowitsch, M. Farlik, C. Bock, T. Rülicke, S. Hippenmeyer,
BioRxiv (n.d.).
date_created: 2026-06-09T08:08:18Z
date_published: 2026-05-05T00:00:00Z
date_updated: 2026-06-16T08:45:25Z
day: '05'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.64898/2026.05.01.722172
ec_funded: 1
fulldoi: https://doi.org/10.64898/2026.05.01.722172
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.05.01.722172
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: bioRxiv
publication_status: submitted
status: public
title: Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously
promotes postnatal neuron survival in cell type specific manner
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21963'
abstract:
- lang: eng
text: The cerebral cortex consists of immense numbers of neuronal and glial cell-types
derived from radial glial progenitor (RGP) cells. How RGPs generate appropriate
quantities of distinct cortical cell-types to safeguard a brain of correct size,
is not well understood. However, genetic aberration in human, including mutations
in PTEN, lead to cortical malformation such as macrocephaly, albeit with unknown
etiology. Here we utilized Mosaic Analysis with Double Markers (MADM)-based clonal
analysis and single cell phenotyping to decipher the role of Pten in neurogenic
and gliogenic RGP lineage progression during cortical ontogeny. While neurogenic
RGP lineage progression and projection neuron production was moderately altered
in the absence of Pten, cortical astrocyte production was drastically increased.
Through genetic epistasis experiments we show that the loss of Pten uncouples
astrocyte generation from essential growth factor signaling hubs, funneling into
MAPK. Collectively, our results suggest that Pten regulates RGP lineage progression
with distinct sequential functions in cortical projection neurogenesis and astrocyte
production to ensure the emergence of a correctly-sized cerebral cortex.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Kay-Uwe Wagner (Wayne State University) for generously
sharing Jak1/2–flox mouse lines; A.\r\nSommer (VBCF GmbH, NGS Unit) for technical
support; N. Kim, V. Mick, S. Schnabl, S. Gobeil, and L.\r\nAndersen for technical
assistance; all members of the Hippenmeyer lab for discussion and B. Novitch for\r\ncomments
on earlier versions of the manuscript. This research was supported by the Scientific
Service Units\r\n(SSU) of IST Austria through resources provided by the Imaging
and Optics Facility (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF).
O.A.M received support from the Austrian Academy of Sciences\r\nÖAW (DOC 186584),
and N.A. from FWF Elise Richter Program (Grant V1041T). This work was also\r\nsupported
by IST Austria institutional funds; FWF SFB F78 (Neuro Stem Modulation) to S.H.,
and the\r\nEuropean Research Council (ERC) under the European Union’s Horizon 2020
research and innovation\r\nprogramme (grant agreement No 725780 LinPro) to S.H."
article_processing_charge: No
author:
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Amarbayasgalan
full_name: Davaatseren, Amarbayasgalan
id: 70ADC922-B424-11E9-99E3-BA18E6697425
last_name: Davaatseren
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Corentine
full_name: Marie, Corentine
last_name: Marie
- first_name: Bassem A.
full_name: Hassan, Bassem A.
last_name: Hassan
- 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: Miranda O, Contreras X, Pauler F, et al. Pten orchestrates neurogenic radial
glia lineage progression and tunes neocortical astrocyte production. bioRxiv.
doi:10.64898/2026.05.01.722191
apa: Miranda, O., Contreras, X., Pauler, F., Davaatseren, A., Amberg, N., Streicher,
C., … Hippenmeyer, S. (n.d.). Pten orchestrates neurogenic radial glia lineage
progression and tunes neocortical astrocyte production. bioRxiv. https://doi.org/10.64898/2026.05.01.722191
chicago: Miranda, Osvaldo, Ximena Contreras, Florian Pauler, Amarbayasgalan Davaatseren,
Nicole Amberg, Carmen Streicher, Ana Villalba Requena, et al. “Pten Orchestrates
Neurogenic Radial Glia Lineage Progression and Tunes Neocortical Astrocyte Production.”
BioRxiv, n.d. https://doi.org/10.64898/2026.05.01.722191.
ieee: O. Miranda et al., “Pten orchestrates neurogenic radial glia lineage
progression and tunes neocortical astrocyte production,” bioRxiv. .
ista: Miranda O, Contreras X, Pauler F, Davaatseren A, Amberg N, Streicher C, Villalba
Requena A, Heger A-M, Marie C, Hassan BA, Rülicke T, Hippenmeyer S. Pten orchestrates
neurogenic radial glia lineage progression and tunes neocortical astrocyte production.
bioRxiv, 10.64898/2026.05.01.722191.
mla: Miranda, Osvaldo, et al. “Pten Orchestrates Neurogenic Radial Glia Lineage
Progression and Tunes Neocortical Astrocyte Production.” BioRxiv, doi:10.64898/2026.05.01.722191.
short: O. Miranda, X. Contreras, F. Pauler, A. Davaatseren, N. Amberg, C. Streicher,
A. Villalba Requena, A.-M. Heger, C. Marie, B.A. Hassan, T. Rülicke, S. Hippenmeyer,
BioRxiv (n.d.).
corr_author: '1'
date_created: 2026-06-09T08:08:53Z
date_published: 2026-05-05T00:00:00Z
date_updated: 2026-06-16T08:57:20Z
day: '05'
ddc:
- '570'
department:
- _id: SiHi
- _id: PreCl
- _id: GradSch
doi: 10.64898/2026.05.01.722191
ec_funded: 1
fulldoi: https://doi.org/10.64898/2026.05.01.722191
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.05.01.722191
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: bioRxiv
publication_status: submitted
status: public
title: Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical
astrocyte production
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22229'
abstract:
- lang: eng
text: Hippocampal CA3 pyramidal neurons (PNs) form the largest autoassociative network
in the mammalian brain. Whether CA3–CA3 recurrent connectivity is genetically
preconfigured or environmentally shaped during ongoing memory storage is currently
unknown. To address this question, we performed multicellular patch-clamp-based
circuit mapping of up to eight CA3 PNs in the mouse hippocampus at multiple postnatal
time points (P7–8, P18–25, and P45–50). Here, we show that the hippocampal CA3
network undergoes a developmental transformation from local, dense, and random
connectivity to a distributed, sparse, and structured configuration. Thus, sparse
and structured connectivity may emerge via experience-dependent mechanisms. In
parallel, the strength of single synapses is downregulated; single synaptic events
are sufficient to trigger postsynaptic spiking early in development, whereas spatial
summation of several inputs is required at later time points. Biologically inspired
models of memory storage by Hebbian synaptic plasticity and retrieval via pattern
completion suggest that developmental changes improve specific aspects of memory
storage and retrieval. Our results imply a developmental transformation of the
neuronal code and the memory functions in the hippocampal CA3 network.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: M-Shop
- _id: ScienComp
acknowledgement: 'We thank Jose Guzman, Simon Hippenmeyer, and Tim Vogels for critically
reading the manuscript, Jozsef Csicsvari for useful discussions, Florian Marr for
technical assistance, and Eleftheria Kralli-Beller for manuscript editing. This
research was supported by the Scientific Services Units (SSUs) of ISTA: the preclinical
facility (PCF) provided housing and breeding of the animals, the imaging and optics
facility (IOF) offered technical training and state of the art equipment, the Miba
machine shop contributed to the construction and maintenance of multicellular recording
setups, and the scientific computing unit helped with the large-scale simulations.
The project received funding from the European Union’s Horizon 2020 research and
innovation programme (ERC Advanced Grants No 692692 GIANTSYN and 101199096 CA3-SYNGRAM
to P.J.; Marie Skłodowska-Curie Grant 754411 to V.V.B.; Marie Skłodowska-Curie Grant
101026635 to J.F.W.), the Fond zur Förderung der Wissenschaftlichen Forschung (P
36232-B, PAT4178023, and 10.55776/CoE16 to P.J.), and the Nomis Foundation (fellowship
to A.N.-O.). V.V.B. received funding from a CONACyT fellowship (289638).'
article_number: '5540'
article_processing_charge: Yes
article_type: original
author:
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Andrea C
full_name: Navas Olivé, Andrea C
id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
last_name: Navas Olivé
orcid: 0000-0002-9280-8597
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. Developmental
emergence of sparse and structured synaptic connectivity in the hippocampal CA3
memory circuit. Nature Communications. 2026;17. doi:10.1038/s41467-026-71914-x
apa: Vargas Barroso, V. M., Watson, J., Navas Olivé, A. C., Schlögl, A., & Jonas,
P. M. (2026). Developmental emergence of sparse and structured synaptic connectivity
in the hippocampal CA3 memory circuit. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-026-71914-x
chicago: Vargas Barroso, Victor M, Jake Watson, Andrea C Navas Olivé, Alois Schlögl,
and Peter M Jonas. “Developmental Emergence of Sparse and Structured Synaptic
Connectivity in the Hippocampal CA3 Memory Circuit.” Nature Communications.
Springer Nature, 2026. https://doi.org/10.1038/s41467-026-71914-x.
ieee: V. M. Vargas Barroso, J. Watson, A. C. Navas Olivé, A. Schlögl, and P. M.
Jonas, “Developmental emergence of sparse and structured synaptic connectivity
in the hippocampal CA3 memory circuit,” Nature Communications, vol. 17.
Springer Nature, 2026.
ista: Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. 2026. Developmental
emergence of sparse and structured synaptic connectivity in the hippocampal CA3
memory circuit. Nature Communications. 17, 5540.
mla: Vargas Barroso, Victor M., et al. “Developmental Emergence of Sparse and Structured
Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” Nature Communications,
vol. 17, 5540, Springer Nature, 2026, doi:10.1038/s41467-026-71914-x.
short: V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas,
Nature Communications 17 (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: Source data are provided with this paper. Additional original
data are available from the corresponding author upon request. Code is available
from https://doi.org/10.15479/AT-ISTA-21442 under the link https://research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz
date_created: 2026-06-30T13:05:52Z
date_published: 2026-06-23T00:00:00Z
date_updated: 2026-07-01T06:47:49Z
day: '23'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1038/s41467-026-71914-x
ec_funded: 1
external_id:
pmid:
- '42014695'
file:
- access_level: open_access
checksum: d0b0093493926985b4c268662ff4d556
content_type: application/pdf
creator: dernst
date_created: 2026-07-01T06:46:06Z
date_updated: 2026-07-01T06:46:06Z
file_id: '22231'
file_name: 2026_NatureComm_VargasBarroso.pdf
file_size: 18304997
relation: main_file
success: 1
file_date_updated: 2026-07-01T06:46:06Z
fulldoi: https://doi.org/10.1038/s41467-026-71914-x
has_accepted_license: '1'
intvolume: ' 17'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: e62b56fe-ab3c-11f0-94c7-d181dd352b3b
grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
grant_number: PAT 4178023
name: Synaptic networks of human brain
- _id: 26366136-B435-11E9-9278-68D0E5697425
name: Reglas de Conectividad funcional en el hipocampo
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '21442'
relation: research_data
status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Developmental emergence of sparse and structured synaptic connectivity in the
hippocampal CA3 memory circuit
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: 17
year: '2026'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22333'
abstract:
- lang: eng
text: RNA polymerase II (Pol II) must be assembled in the cytoplasm before it enters
the nucleus, where it transcribes protein-coding genes. Although transcription
by Pol II is intensively studied, how this central multi-subunit enzyme is made
and the role of dedicated assembly factors remains unclear. Here, we report the
integrative structural analysis of a native human Pol II from the cytoplasm captured
near the end of biogenesis. The complex contains Gdown1 and three biogenesis factors
– RPAP2 and the critical small GTPases GPN1 and GPN3. Cryo-EM analysis of the
complex reveals how Gdown1 and RPAP2 associate with Pol II and prevent the premature
association of transcription factors. Further biochemical and cryo-EM analysis
reveals how RPAP2 tethers GPN1–GPN3 to the complex and how the assembly of the
RPAP2–GPN1–GPN3 complex is controlled by GTP hydrolysis. The combined results
uncover a network of interactions that chaperone cytoplasmic Pol II to prevent
aberrant interactions, reveal a molecular switch regulating biogenesis factor
association, and suggest a general mechanism for the action of GPN-loop GTPase
family of enzymes.
acknowledged_ssus:
- _id: LifeSc
- _id: EM-Fac
- _id: ScienComp
- _id: PreCl
acknowledgement: We thank A. Salmazo for assistance with Pol II purification. We thank
staff at the Vienna BioCenter Core Facilities (VBCF) Proteomics facility for immunoprecipitation-mass
spectrometry analysis, and J.A. Stopp for assistance with IP-MS data visualization.
This research was further supported by the Scientific Service Units (SSUs) of ISTA
through resources provided by the Lab Support Facility (LSF), Electron Microscopy
Facility (EMF), Scientific Computing (SciComp), and the Preclinical Facility (PCF).
F.H. was funded by the Endowed Professorship of the Lower Austria Research Funding
Agency (GFF NÖ) and by the Austrian Research Promotion Agency (FFG) through the
COIN Establishment Grant n.o. 45624401.
article_processing_charge: Yes
article_type: original
author:
- first_name: Annamaria
full_name: Hlavata, Annamaria
id: 36062FEC-F248-11E8-B48F-1D18A9856A87
last_name: Hlavata
- first_name: Benjamin
full_name: Neuditschko, Benjamin
last_name: Neuditschko
- first_name: Ulla
full_name: Schellhaas, Ulla
last_name: Schellhaas
- first_name: Clemens
full_name: Plaschka, Clemens
last_name: Plaschka
- first_name: Franz
full_name: Herzog, Franz
last_name: Herzog
- first_name: Carrie A
full_name: Bernecky, Carrie A
id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
last_name: Bernecky
orcid: 0000-0003-0893-7036
biorxivid: 1
citation:
ama: Hlavata A, Neuditschko B, Schellhaas U, Plaschka C, Herzog F, Bernecky C. Structure
of cytoplasmic RNA polymerase II. Nature Communications. 2026. doi:10.1038/s41467-026-75416-8
apa: Hlavata, A., Neuditschko, B., Schellhaas, U., Plaschka, C., Herzog, F., &
Bernecky, C. (2026). Structure of cytoplasmic RNA polymerase II. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-026-75416-8
chicago: Hlavata, Annamaria, Benjamin Neuditschko, Ulla Schellhaas, Clemens Plaschka,
Franz Herzog, and Carrie Bernecky. “Structure of Cytoplasmic RNA Polymerase II.”
Nature Communications. Springer Nature, 2026. https://doi.org/10.1038/s41467-026-75416-8.
ieee: A. Hlavata, B. Neuditschko, U. Schellhaas, C. Plaschka, F. Herzog, and C.
Bernecky, “Structure of cytoplasmic RNA polymerase II,” Nature Communications.
Springer Nature, 2026.
ista: Hlavata A, Neuditschko B, Schellhaas U, Plaschka C, Herzog F, Bernecky C.
2026. Structure of cytoplasmic RNA polymerase II. Nature Communications.
mla: Hlavata, Annamaria, et al. “Structure of Cytoplasmic RNA Polymerase II.” Nature
Communications, Springer Nature, 2026, doi:10.1038/s41467-026-75416-8.
short: A. Hlavata, B. Neuditschko, U. Schellhaas, C. Plaschka, F. Herzog, C. Bernecky,
Nature Communications (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: "The\r\nc ryo EM maps generated in this study were deposited
to the EM Data Bank under the\r\naccession codes: EMD 55583 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
55583\r\n(Pol II Gdown1 RPAP2 composite map), EMD 55578\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
55578 Pol II Gdown1 RPAP2 Pol II core\r\nmap EMD 55579 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
55579 Pol II\r\nGdown1 RPAP2 Pol II stalk map EMD 55580\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
55580 Pol II Gdown1 RPAP2 RPAP2\r\nmap EMD 55581 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
55 581 Pol II\r\nGdown1 RPAP2 Gdown1 N terminus map EMD 55582\r\n[https://www.ebi.ac.uk/pdbe/entry/emdb/EMD
55582 Pol II Gdown1 RPAP2 Gdown1\r\nC terminus map and EMD 55585 [https://www.ebi.ac.uk/pdbe/entry/emdb/EMD\r\n55585
RPAP2 GPN1 GPN3 map Model coordi nates were deposited to the PDBe under\r\nthe accession
codes: 9T5H [http://doi.org/10.2210/pdb 9T5H / (Pol II Gdown1\r\nRPAP2 complex structure)
and 9T5J [http://doi.org/10.2210/pdb 9T5H / (GPN1\r\nGPN3 RPAP2 structure). Immunoprecipitation
mass spectrometry and crosslinking mass\r\nspectrometry proteomics data have been
deposited to the ProteomeXchange Consortium\r\nvia the PRIDE partner repository
with the dataset identifiers PXD071638\r\n[http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD
071638 and\r\nP XD070852\r\n[http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD
070852\r\nAlphaFold3 structure predictions have been deposited to the Zenodo repository\r\nhttps://doi.org/10.5281/zenodo.20687910
P reviously published model coordinates\r\nwere utilized and are available at the
PDB under the accession codes 8QEP\r\n[http://doi.org/10.2210/pdb 8QEP / 9BZ 0 [http://doi.org/10.2210/pdb
9BZ 0 /\r\nand 7B7U [http://doi.org/10.2210/pdb 7B7U / Source Data are provided
with this\r\npaper."
date_created: 2026-07-14T07:27:59Z
date_published: 2026-07-13T00:00:00Z
date_updated: 2026-07-16T11:29:31Z
day: '13'
ddc:
- '570'
department:
- _id: CaBe
doi: 10.1038/s41467-026-75416-8
external_id:
biorxivid:
- 10.64898/2025.12.10.692585
fulldoi: https://doi.org/10.1038/s41467-026-75416-8
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41467-026-75416-8
month: '07'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Structure of cytoplasmic RNA polymerase II
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
year: '2026'
...
---
OA_place: repository
_id: '22704'
abstract:
- lang: eng
text: "The medial habenula (MHb) is implicated in regulating emotional responses
to aversive events. Studies in zebrafish have identified a remarkable morphological
left–right asymmetry in the dorsal habenula (zebrafish equivalent of mammalian
MHb)-interpeduncular nucleus (IPN) pathway and its asymmetrical roles in behavior.
However, there is little evidence for structural or functional lateralization
in the mammalian MHb-IPN pathway. Here, we investigated the synaptic properties
of left- and right-MHb afferents to the IPN and their roles in the expression
of conditioned fear in mice. We found that each IPN neuron receives inputs from
both left and right MHb, but the left MHb-originating synapses exhibit lower release
probability and higher γ-aminobutyric acid type B receptor (GABABR)-mediated potentiation
compared to the right MHb-originating synapses. Interestingly, these asymmetrical
properties persist in the inversus visceral mutant mice with normal internal organ
laterality (situs solitus), but nearly disappear in those with reversed internal
organ laterality (situs inversus). Behaviorally, chemogenetic inhibition of cholinergic
neurons and conditional deletion of GABABR in the left, but not the right, MHb
significantly attenuated cue-dependent fear recall. Our results demonstrate functional
asymmetry of the MHb under partial influence of the nodal flow in mice, revealing
a predominant role of GABABR-mediated signaling in the left MHb-IPN pathway in
modulating fear memories. These findings suggest that lateralized MHb pathways
could represent a fundamental principle in the neural regulation of emotion across
species but that they develop differently in zebrafish and mice.\r\n"
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
article_processing_charge: No
author:
- first_name: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- first_name: Cihan
full_name: Önal, Cihan
last_name: Önal
citation:
ama: Le Monnier E, Önal C. Asymmetrical modulation of fear expression via GABAB
receptors in the mouse medial habenula. 2026. doi:10.15479/AT-ISTA-22704
apa: Le Monnier, E., & Önal, C. (2026). Asymmetrical modulation of fear expression
via GABAB receptors in the mouse medial habenula. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT-ISTA-22704
chicago: Le Monnier, Elodie, and Cihan Önal. “Asymmetrical Modulation of Fear Expression
via GABAB Receptors in the Mouse Medial Habenula.” Institute of Science and Technology
Austria, 2026. https://doi.org/10.15479/AT-ISTA-22704.
ieee: E. Le Monnier and C. Önal, “Asymmetrical modulation of fear expression via
GABAB receptors in the mouse medial habenula.” Institute of Science and Technology
Austria, 2026.
ista: Le Monnier E, Önal C. 2026. Asymmetrical modulation of fear expression via
GABAB receptors in the mouse medial habenula, Institute of Science and Technology
Austria, 10.15479/AT-ISTA-22704.
mla: Le Monnier, Elodie, and Cihan Önal. Asymmetrical Modulation of Fear Expression
via GABAB Receptors in the Mouse Medial Habenula. Institute of Science and
Technology Austria, 2026, doi:10.15479/AT-ISTA-22704.
short: E. Le Monnier, C. Önal, (2026).
corr_author: '1'
date_created: 2026-08-13T12:20:08Z
date_published: 2026-08-13T00:00:00Z
date_updated: 2026-08-13T13:30:37Z
day: '13'
department:
- _id: RySh
doi: 10.15479/AT-ISTA-22704
doi_confirm: '1'
ec_funded: 1
file:
- access_level: open_access
checksum: 7742bb211a43bb87c2b5ce7bda3068ae
content_type: application/x-zip-compressed
creator: elemonni
date_created: 2026-08-13T12:07:53Z
date_updated: 2026-08-13T12:07:53Z
file_id: '22705'
file_name: Behavior.zip
file_size: 162086
relation: main_file
success: 1
- access_level: open_access
checksum: a162eb6103a770d94536374e02934fcf
content_type: application/x-zip-compressed
creator: elemonni
date_created: 2026-08-13T12:07:57Z
date_updated: 2026-08-13T12:07:57Z
file_id: '22706'
file_name: image_analysis.zip
file_size: 6643
relation: main_file
success: 1
- access_level: open_access
checksum: 608aaf395bba5fd9cf62d8c8940d63aa
content_type: application/x-zip-compressed
creator: elemonni
date_created: 2026-08-13T12:07:59Z
date_updated: 2026-08-13T12:07:59Z
file_id: '22707'
file_name: Recordings.zip
file_size: 1193016
relation: main_file
success: 1
- access_level: open_access
checksum: 2389ebd71238bd7de03d20504a8cf962
content_type: text/plain
creator: elemonni
date_created: 2026-08-13T13:06:29Z
date_updated: 2026-08-13T13:06:29Z
file_id: '22708'
file_name: README.txt
file_size: 246
relation: main_file
success: 1
file_date_updated: 2026-08-13T13:06:29Z
fulldoi: https://doi.org/10.15479/AT-ISTA-22704
has_accepted_license: '1'
month: '08'
oa: 1
oa_version: None
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 92503f6e-16d5-11f0-9cad-8c571927f3b7
grant_number: PAT 5720324
name: New regime of presynaptic release regulation
publisher: Institute of Science and Technology Austria
status: public
title: Asymmetrical modulation of fear expression via GABAB receptors in the mouse
medial habenula
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: research_data
user_id: 68b8ca59-c5b3-11ee-8790-cd641c68093d
year: '2026'
...
---
OA_place: publisher
_id: '22735'
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
- _id: Bio
acknowledgement: "This project was supported by the following funding agencies: ERC
under the European\r\nUnion's Horizon 2020 research and innovation program (ERC
Advanced Grants No 692692\r\n“GIANTSYN” and 101199096 “CA3-SYNGRAM” to P.J.), the
Fonds zur Förderung der\r\nwissenschaftlichen Forschung (P 36232-B, stand-alone
grant, PAT 4178023, principal\r\ninvestigator project, and 10.55776/CoE 16 “GABA
neurons” to P.J.), and the European Union’s\r\nHorizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant\r\nagreement (No 101034413, to
K.L.)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Peipeng
full_name: Lin, Peipeng
id: 7E3060D0-A92C-11E9-A326-26C8E5697425
last_name: Lin
citation:
ama: 'Lin P. Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses. 2026. doi:10.15479/AT-ISTA-22735'
apa: 'Lin, P. (2026). Calibrating the teacher synapse: Mechanisms and functional
significance of presynaptic inhibition at hippocampal mossy fiber synapses.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-22735'
chicago: 'Lin, Peipeng. “Calibrating the Teacher Synapse: Mechanisms and Functional
Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.” Institute
of Science and Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-22735.'
ieee: 'P. Lin, “Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses,” Institute of Science
and Technology Austria, 2026.'
ista: 'Lin P. 2026. Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses. Institute of Science
and Technology Austria.'
mla: 'Lin, Peipeng. Calibrating the Teacher Synapse: Mechanisms and Functional
Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.
Institute of Science and Technology Austria, 2026, doi:10.15479/AT-ISTA-22735.'
short: 'P. Lin, Calibrating the Teacher Synapse: Mechanisms and Functional Significance
of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses, Institute of Science
and Technology Austria, 2026.'
corr_author: '1'
das_tickbox: '0'
date_created: 2026-08-18T15:23:41Z
date_published: 2026-08-25T00:00:00Z
date_updated: 2026-08-31T11:11:55Z
day: '25'
ddc:
- '571'
- '573'
degree_awarded: PhD
department:
- _id: GradSch
- _id: PeJo
doi: 10.15479/AT-ISTA-22735
doi_confirm: '1'
ec_funded: 1
file:
- access_level: closed
checksum: 13cc7ead72aad90a134f310b531c73cd
content_type: application/pdf
creator: plin
date_created: 2026-08-26T10:09:48Z
date_updated: 2026-08-26T10:09:48Z
embargo: 2027-09-01
embargo_to: open_access
file_id: '22765'
file_name: 2026_Lin_Peipeng_Thesis.pdf
file_size: 6376229
relation: main_file
- access_level: closed
checksum: 8c9c1445a7df284377be1a8c9dadd7c5
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: plin
date_created: 2026-08-26T10:09:53Z
date_updated: 2026-08-26T10:09:53Z
file_id: '22766'
file_name: 2026_Lin_Peipeng_Thesis.docx
file_size: 17681883
relation: source_file
file_date_updated: 2026-08-26T10:09:53Z
fulldoi: https://doi.org/10.15479/AT-ISTA-22735
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa_version: Published Version
page: '88'
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: e62b56fe-ab3c-11f0-94c7-d181dd352b3b
grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
grant_number: PAT 4178023
name: Synaptic networks of human brain
- _id: fc2ed2f7-9c52-11eb-aca3-c01059dda49c
call_identifier: H2020
grant_number: '101034413'
name: 'IST-BRIDGE: International postdoctoral program'
publication_identifier:
isbn:
- 978-3-99078-088-6
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
researchdata_availability: upon request
status: public
supervisor:
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
supplementarymaterial: yes
title: 'Calibrating the teacher synapse: Mechanisms and functional significance of
presynaptic inhibition at hippocampal mossy fiber synapses'
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: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22753'
abstract:
- lang: eng
text: Radial glial progenitors (RGPs) produce all excitatory neurons in the developing
cerebral cortex. Mosaic analysis with double markers (MADM)-based lineage tracing
in vivo has revealed a quantitative framework of RGP lineage progression1. Here
we established MADM technology2,3 in mouse embryonic stem cells to probe RGP lineage
progression in a self-organizing cortical organoid system. We found that RGPs
exhibit a high level of plasticity in proliferative potential in organoids rather
than strict temporally stereotyped lineage progression as observed in vivo. RGPs
in organoids showed increased lineage restriction, diminishing cell-type diversity
in clones of cortical projection neurons, despite uniform single-cell transcriptional
signatures of RGPs and a unitary lineage trajectory. Thus, critical non-cell-autonomous
cues that are absent in self-organizing systems and/or the genuine stem cell niche
are essential for faithful temporal control of RGP lineage progression and the
generation of clonal cortical cell-type diversity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank M. L. de Guevara, S. Jayaram and A. Heger for technical
assistance with mESC derivation; M. Goudarzi for assistance with organoid imaging;
M. Leeb and F. Freeman for advice in culturing mESCs and organoids; S. Gobeil and
L. Sweeney for reagents and advice for organoid clearing; A. Heger for mouse colony
management; J. Hauser for technical assistance; the Stanford Brain Organogenesis
Workshop; and all members of the Hippenmeyer laboratory for discussion and/or comments
on the manuscript. This study was supported by the Scientific Service Units (SSU)
of the Institute of Science and Technology, Austria through resources provided by
the Imaging and Optics Facility (IOF), Laboratory Support Facility (LSF) and Preclinical
Facility (PCF). M.S. received funding from the European Commission (IST plus postdoctoral
fellowship). This work was supported by ISTA institutional funds to S.H., FWF SFB
F78 Neuro Stem Modulation to S.H., and by the European Research Council (ERC) under
the European Union’s Horizon 2020 Research And Innovation Program (grant agreement
725780 LinPro) to S.H. 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: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Fabrizia
full_name: Pipicelli, Fabrizia
id: 649134fd-d012-11ed-8f82-db1e5050f9ba
last_name: Pipicelli
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Stouffer MA, Miranda O, Pauler F, et al. Temporal uncoupling of radial glia
lineage progression in cortical organoids. Nature. 2026. doi:10.1038/s41586-026-10916-7
apa: Stouffer, M. A., Miranda, O., Pauler, F., Pipicelli, F., Streicher, C., Cheung,
G. T., & Hippenmeyer, S. (2026). Temporal uncoupling of radial glia lineage
progression in cortical organoids. Nature. Springer Nature. https://doi.org/10.1038/s41586-026-10916-7
chicago: Stouffer, Melissa A, Osvaldo Miranda, Florian Pauler, Fabrizia Pipicelli,
Carmen Streicher, Giselle T Cheung, and Simon Hippenmeyer. “Temporal Uncoupling
of Radial Glia Lineage Progression in Cortical Organoids.” Nature. Springer
Nature, 2026. https://doi.org/10.1038/s41586-026-10916-7.
ieee: M. A. Stouffer et al., “Temporal uncoupling of radial glia lineage
progression in cortical organoids,” Nature. Springer Nature, 2026.
ista: Stouffer MA, Miranda O, Pauler F, Pipicelli F, Streicher C, Cheung GT, Hippenmeyer
S. 2026. Temporal uncoupling of radial glia lineage progression in cortical organoids.
Nature.
mla: Stouffer, Melissa A., et al. “Temporal Uncoupling of Radial Glia Lineage Progression
in Cortical Organoids.” Nature, Springer Nature, 2026, doi:10.1038/s41586-026-10916-7.
short: M.A. Stouffer, O. Miranda, F. Pauler, F. Pipicelli, C. Streicher, G.T. Cheung,
S. Hippenmeyer, Nature (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: All data generated and analysed in this study are included
in the paper, source data and/or Supplementary Tables 2 and 3. Raw sequencing data
have been deposited with Gene Expression Omnibus (GEO) accession number GSE327470.
Source data are provided with this paper. All scripts used to prepare data and figures
for this manuscript are accessible on GitHub at https://github.com/fpauler/Temporal-Uncoupling-of-Radial-Glia-Lineage-Progression-in-Cortical-Organoid.
date_created: 2026-08-23T22:01:47Z
date_published: 2026-08-12T00:00:00Z
date_updated: 2026-09-09T07:11:02Z
day: '12'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41586-026-10916-7
ec_funded: 1
external_id:
pmid:
- '42587153'
file:
- access_level: open_access
checksum: 11383e28fc430b28d2666f73833e8b56
content_type: application/pdf
creator: dernst
date_created: 2026-09-07T13:24:10Z
date_updated: 2026-09-07T13:24:10Z
file_id: '22844'
file_name: 2026_Nature_Stouffer.pdf
file_size: 48513068
relation: main_file
success: 1
file_date_updated: 2026-09-07T13:24:10Z
fulldoi: https://doi.org/10.1038/s41586-026-10916-7
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Temporal uncoupling of radial glia lineage progression in cortical organoids
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
year: '2026'
...
---
OA_place: repository
OA_type: gold
_id: '18697'
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
labelling. 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: Bio
- _id: LifeSc
- _id: ScienComp
- _id: PreCl
- _id: M-Shop
- _id: E-Lib
article_processing_charge: No
author:
- 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: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
citation:
ama: Danzl JG, Lyudchik J, Kreuzinger C. Light-microscopy based connectomic reconstruction
of mammalian brain tissue. 2025. doi:10.15479/AT:ISTA:18697
apa: Danzl, J. G., Lyudchik, J., & Kreuzinger, C. (2025). Light-microscopy based
connectomic reconstruction of mammalian brain tissue. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT:ISTA:18697
chicago: Danzl, Johann G, Julia Lyudchik, and Caroline Kreuzinger. “Light-Microscopy
Based Connectomic Reconstruction of Mammalian Brain Tissue.” Institute of Science
and Technology Austria, 2025. https://doi.org/10.15479/AT:ISTA:18697.
ieee: J. G. Danzl, J. Lyudchik, and C. Kreuzinger, “Light-microscopy based connectomic
reconstruction of mammalian brain tissue.” Institute of Science and Technology
Austria, 2025.
ista: Danzl JG, Lyudchik J, Kreuzinger C. 2025. Light-microscopy based connectomic
reconstruction of mammalian brain tissue, Institute of Science and Technology
Austria, 10.15479/AT:ISTA:18697.
mla: Danzl, Johann G., et al. Light-Microscopy Based Connectomic Reconstruction
of Mammalian Brain Tissue. Institute of Science and Technology Austria, 2025,
doi:10.15479/AT:ISTA:18697.
short: J.G. Danzl, J. Lyudchik, C. Kreuzinger, (2025).
contributor:
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first_name: Jakob
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first_name: Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
corr_author: '1'
date_created: 2024-12-20T09:22:20Z
date_published: 2025-03-03T00:00:00Z
date_updated: 2026-04-28T13:33:34Z
day: '03'
ddc:
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status: public
title: Light-microscopy based connectomic reconstruction of mammalian brain tissue
tmp:
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legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
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...
---
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abstract:
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text: Transcription by RNA polymerase II (Pol II) can be repressed by noncoding
RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs
repress transcription remains unclear. Here we present cryogenic-electron microscopy
structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA
and RNA bind to Pol II during transcription elongation. Further, we show how distinct
domains of the general transcription factor TFIIF control repressive activity.
Together, we reveal how a noncoding RNA can regulate mammalian gene expression.
acknowledged_ssus:
- _id: LifeSc
- _id: EM-Fac
- _id: ScienComp
- _id: PreCl
acknowledgement: We thank the members of the Bernecky laboratory for helpful discussions
and A. Hlavata for providing Pol II for use in the fluorescence anisotropy binding
assay. We thank V.-V. Hodirnau for SerialEM data collection and support with EPU
data collection. We thank D. Slade (Max Perutz Laboratories and Medical University
of Vienna, Vienna, Austria) for the wild-type TFIIF expression plasmid. We thank
N. Thompson and R. Burgess (McArdle Laboratory for Cancer Research, University of
Wisconsin-Madison, Madison, WI, USA) for the 8WG16 hybridoma cell line. We thank
C. Plaschka and M. Loose for critical reading of the manuscript. This work was supported
by Austrian Science Fund (FWF) grant no. P34185 (DOI 10.55776/P34185) (C.B.). The
funders had no role in study design, data collection and analysis, decision to publish
or preparation of the manuscript. This research was further supported by the Scientific
Service Units of ISTA through resources provided by the Laboratory Support Facility,
Electron Microscopy Facility, Scientific Computing and the Preclinical Facility.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Katarina
full_name: Tluckova, Katarina
id: 4AC7D980-F248-11E8-B48F-1D18A9856A87
last_name: Tluckova
- first_name: Beata M
full_name: Kaczmarek, Beata M
id: 36FA4AFA-F248-11E8-B48F-1D18A9856A87
last_name: Kaczmarek
- first_name: Anita P
full_name: Testa Salmazo, Anita P
id: 41F1F098-F248-11E8-B48F-1D18A9856A87
last_name: Testa Salmazo
- first_name: Carrie A
full_name: Bernecky, Carrie A
id: 2CB9DFE2-F248-11E8-B48F-1D18A9856A87
last_name: Bernecky
orcid: 0000-0003-0893-7036
citation:
ama: Tluckova K, Kaczmarek BM, Testa Salmazo AP, Bernecky C. Mechanism of mammalian
transcriptional repression by noncoding RNA. Nature Structural & Molecular
Biology. 2025;32:607-612. doi:10.1038/s41594-024-01448-7
apa: Tluckova, K., Kaczmarek, B. M., Testa Salmazo, A. P., & Bernecky, C. (2025).
Mechanism of mammalian transcriptional repression by noncoding RNA. Nature
Structural & Molecular Biology. Springer Nature. https://doi.org/10.1038/s41594-024-01448-7
chicago: Tluckova, Katarina, Beata M Kaczmarek, Anita P Testa Salmazo, and Carrie
Bernecky. “Mechanism of Mammalian Transcriptional Repression by Noncoding RNA.”
Nature Structural & Molecular Biology. Springer Nature, 2025. https://doi.org/10.1038/s41594-024-01448-7.
ieee: K. Tluckova, B. M. Kaczmarek, A. P. Testa Salmazo, and C. Bernecky, “Mechanism
of mammalian transcriptional repression by noncoding RNA,” Nature Structural
& Molecular Biology, vol. 32. Springer Nature, pp. 607–612, 2025.
ista: Tluckova K, Kaczmarek BM, Testa Salmazo AP, Bernecky C. 2025. Mechanism of
mammalian transcriptional repression by noncoding RNA. Nature Structural &
Molecular Biology. 32, 607–612.
mla: Tluckova, Katarina, et al. “Mechanism of Mammalian Transcriptional Repression
by Noncoding RNA.” Nature Structural & Molecular Biology, vol. 32,
Springer Nature, 2025, pp. 607–12, doi:10.1038/s41594-024-01448-7.
short: K. Tluckova, B.M. Kaczmarek, A.P. Testa Salmazo, C. Bernecky, Nature Structural
& Molecular Biology 32 (2025) 607–612.
corr_author: '1'
date_created: 2025-01-08T11:20:20Z
date_published: 2025-04-01T00:00:00Z
date_updated: 2025-11-20T10:28:36Z
day: '01'
ddc:
- '570'
department:
- _id: CaBe
doi: 10.1038/s41594-024-01448-7
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pmid:
- '39762629'
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creator: dernst
date_created: 2025-04-16T08:17:27Z
date_updated: 2025-04-16T08:17:27Z
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file_size: 9306639
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success: 1
file_date_updated: 2025-04-16T08:17:27Z
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isi: 1
language:
- iso: eng
month: '04'
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oa_version: Published Version
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title: Mechanism of mammalian transcriptional repression by noncoding RNA
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: 32
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18879'
abstract:
- lang: eng
text: 'Our brain has remarkable computational power, generating sophisticated behaviors,
storing memories over an individual’s lifetime, and producing higher cognitive
functions. However, little of our neuroscience knowledge covers the human brain.
Is this organ truly unique, or is it a scaled version of the extensively studied
rodent brain? Combining multicellular patch-clamp recording with expansion-based
superresolution microscopy and full-scale modeling, we determined the cellular
and microcircuit properties of the human hippocampal CA3 region, a fundamental
circuit for memory storage. In contrast to neocortical networks, human hippocampal
CA3 displayed sparse connectivity, providing a circuit architecture that maximizes
associational power. Human synapses showed unique reliability, high precision,
and long integration times, exhibiting both species- and circuit-specific properties.
Together with expanded neuronal numbers, these circuit characteristics greatly
enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit
properties of the human hippocampus and begin to unravel the inner workings of
our most complex organ. '
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: ScienComp
acknowledgement: We thank Florian Marr for excellent technical assistance, Christina
Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor
Asenov for development of the transportation box for human brain tissue, Tim Vogels
for guidance on simulations, Marcus Huber for mathematical advice, Walter Kaufmann
for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript
editing. This research was supported by the Scientific Services Units (SSUs) of
ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and
Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop,
and Scientific Computing. We are particularly grateful to the patient donors for
their support of this project and also acknowledge the excellent support of the
Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger
and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division
of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha
Feucht, and Ekaterina Pataraia for their clinical care of the patients included
in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample
donors for their support of this research. The project received funding from the
European Research Council (ERC) under the European Union’s Horizon 2020 research
and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie
Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
(FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian
Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship
(to A.N.-O.).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Rebecca
full_name: Morse, Rebecca
id: ceb89ae7-dc8d-11ea-abe3-da3301d0eab4
last_name: Morse
- first_name: Andrea C
full_name: Navas Olivé, Andrea C
id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
last_name: Navas Olivé
orcid: 0000-0002-9280-8597
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
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full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Matthias
full_name: Tomschik, Matthias
last_name: Tomschik
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Watson J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific
functional connectivity rules for efficient associative memory. Cell. 2025;188(2):501-514.e18.
doi:10.1016/j.cell.2024.11.022
apa: Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli,
M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. Cell. Elsevier. https://doi.org/10.1016/j.cell.2024.11.022
chicago: Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé,
Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M
Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for
Efficient Associative Memory.” Cell. Elsevier, 2025. https://doi.org/10.1016/j.cell.2024.11.022.
ieee: J. Watson et al., “Human hippocampal CA3 uses specific functional connectivity
rules for efficient associative memory,” Cell, vol. 188, no. 2. Elsevier,
p. 501–514.e18, 2025.
ista: Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG,
Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.
mla: Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
Rules for Efficient Associative Memory.” Cell, vol. 188, no. 2, Elsevier,
2025, p. 501–514.e18, doi:10.1016/j.cell.2024.11.022.
short: J. Watson, V.M. Vargas Barroso, R. Morse, A.C. Navas Olivé, M. Tavakoli,
J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, Cell 188 (2025) 501–514.e18.
corr_author: '1'
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date_updated: 2026-04-14T08:34:32Z
day: '23'
ddc:
- '570'
department:
- _id: JoDa
- _id: PeJo
- _id: GradSch
doi: 10.1016/j.cell.2024.11.022
ec_funded: 1
external_id:
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title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
associative memory
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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
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year: '2025'
...
---
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_id: '18991'
abstract:
- lang: eng
text: Research data for the article "Learning reshapes the hippocampal representation
hierarchy" from Chiossi et al. (PNAS, 2025). The data includes hippocampal CA1
unit activity and behaviour tracking of 5 Long Evans rats during the learning
of an associative memory task. Detailed information can be found in the 'readme.txt'
file.
acknowledged_ssus:
- _id: PreCl
- _id: M-Shop
acknowledgement: Thanks to Rebecca Morse for performing one of the experiments under
H.S.C.C. supervision and Jago Wallenschus for technical support, especially with
maze design.
article_processing_charge: No
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full_name: Chiossi, Heloisa
id: 2BBA502C-F248-11E8-B48F-1D18A9856A87
last_name: Chiossi
orcid: 0009-0004-2973-278X
citation:
ama: Chiossi HSC. Research data for the publication “Learning reshapes the hippocampal
representation hierarchy.” 2025. doi:10.15479/AT:ISTA:18991
apa: Chiossi, H. S. C. (2025). Research data for the publication “Learning reshapes
the hippocampal representation hierarchy.” Institute of Science and Technology
Austria. https://doi.org/10.15479/AT:ISTA:18991
chicago: Chiossi, Heloisa S. C. “Research Data for the Publication ‘Learning Reshapes
the Hippocampal Representation Hierarchy.’” Institute of Science and Technology
Austria, 2025. https://doi.org/10.15479/AT:ISTA:18991.
ieee: H. S. C. Chiossi, “Research data for the publication ‘Learning reshapes the
hippocampal representation hierarchy.’” Institute of Science and Technology Austria,
2025.
ista: Chiossi HSC. 2025. Research data for the publication ‘Learning reshapes the
hippocampal representation hierarchy’, Institute of Science and Technology Austria,
10.15479/AT:ISTA:18991.
mla: Chiossi, Heloisa S. C. Research Data for the Publication “Learning Reshapes
the Hippocampal Representation Hierarchy.” Institute of Science and Technology
Austria, 2025, doi:10.15479/AT:ISTA:18991.
short: H.S.C. Chiossi, (2025).
contributor:
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first_name: Michele
id: 30BD0376-F248-11E8-B48F-1D18A9856A87
last_name: Nardin
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id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
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first_name: Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
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status: public
title: Research data for the publication "Learning reshapes the hippocampal representation
hierarchy"
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
_id: '19076'
abstract:
- lang: eng
text: For accurate perception and motor control, an animal must distinguish between
sensory experiences elicited by external stimuli and those elicited by its own
actions. The diversity of behaviors and their complex influences on the senses
make this distinction challenging. Here, we uncover an action–cue hub that coordinates
motor commands with visual processing in the brain’s first visual relay. We show
that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge
center, integrating visual translational optic flow signals with motor copies
from saccades, locomotion and pupil dynamics. The vLGN relays these signals to
correct action-specific visual distortions and to refine perception, as shown
for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide
vLGN projections drive corrective actions necessary for accurate visuomotor control.
Our results reveal an extended corollary discharge architecture that refines early
visual transformations and coordinates actions via a distributed hub-and-spoke
network to enable visual perception during action.
acknowledged_ssus:
- _id: ScienComp
- _id: PreCl
- _id: LifeSc
- _id: Bio
acknowledgement: We thank Y. Ben-Simon for generously making viral vectors for retrograde
tracing available, as well as J. Watson and F. Marr for reagents. We also thank
R. Shigemoto, W. Młynarski and members of the Neuroethology group for their comments
on the manuscript and L. Burnett for her schematic drawings. This research was supported
by the Scientific Service Units of ISTA through resources provided by Scientific
Computing, the Preclinical Facility, the Lab Support Facility and the Imaging and
Optics Facility, in particular F. Lange, M. Schunn and T. Asenov. This work was
supported by European Research Council Starting Grant no. 756502 (M.J.) and European
Research Council Consolidator Grant no. 101086580 (M.J.); and EMBO ALTF grant no.
1098-2017 (A.S.) and Human Frontiers Science Program grant no. LT000256/2018-L (A.S.).
Open access funding provided by Institute of Science and Technology (IST Austria).
article_number: '7278'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Tomas A
full_name: Vega Zuniga, Tomas A
id: 2E7C4E78-F248-11E8-B48F-1D18A9856A87
last_name: Vega Zuniga
- first_name: Anton L
full_name: Sumser, Anton L
id: 3320A096-F248-11E8-B48F-1D18A9856A87
last_name: Sumser
orcid: 0000-0002-4792-1881
- first_name: Olga
full_name: Symonova, Olga
id: 3C0C7BC6-F248-11E8-B48F-1D18A9856A87
last_name: Symonova
orcid: 0000-0003-2012-9947
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Florian
full_name: Schmidt, Florian
id: A2EF226A-AF19-11E9-924C-0525E6697425
last_name: Schmidt
- first_name: Maximilian A
full_name: Jösch, Maximilian A
id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
last_name: Jösch
orcid: 0000-0002-3937-1330
citation:
ama: Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA.
A thalamic hub-and-spoke network enables visual perception during action by coordinating
visuomotor dynamics. Nature Neuroscience. 2025;28. doi:10.1038/s41593-025-01874-w
apa: Vega Zuniga, T. A., Sumser, A. L., Symonova, O., Koppensteiner, P., Schmidt,
F., & Jösch, M. A. (2025). A thalamic hub-and-spoke network enables visual
perception during action by coordinating visuomotor dynamics. Nature Neuroscience.
Springer Nature. https://doi.org/10.1038/s41593-025-01874-w
chicago: Vega Zuniga, Tomas A, Anton L Sumser, Olga Symonova, Peter Koppensteiner,
Florian Schmidt, and Maximilian A Jösch. “A Thalamic Hub-and-Spoke Network Enables
Visual Perception during Action by Coordinating Visuomotor Dynamics.” Nature
Neuroscience. Springer Nature, 2025. https://doi.org/10.1038/s41593-025-01874-w.
ieee: T. A. Vega Zuniga, A. L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
and M. A. Jösch, “A thalamic hub-and-spoke network enables visual perception during
action by coordinating visuomotor dynamics,” Nature Neuroscience, vol.
28. Springer Nature, 2025.
ista: Vega Zuniga TA, Sumser AL, Symonova O, Koppensteiner P, Schmidt F, Jösch MA.
2025. A thalamic hub-and-spoke network enables visual perception during action
by coordinating visuomotor dynamics. Nature Neuroscience. 28, 7278.
mla: Vega Zuniga, Tomas A., et al. “A Thalamic Hub-and-Spoke Network Enables Visual
Perception during Action by Coordinating Visuomotor Dynamics.” Nature Neuroscience,
vol. 28, 7278, Springer Nature, 2025, doi:10.1038/s41593-025-01874-w.
short: T.A. Vega Zuniga, A.L. Sumser, O. Symonova, P. Koppensteiner, F. Schmidt,
M.A. Jösch, Nature Neuroscience 28 (2025).
corr_author: '1'
date_created: 2025-02-23T23:01:58Z
date_published: 2025-03-01T00:00:00Z
date_updated: 2026-06-18T18:12:08Z
day: '01'
ddc:
- '570'
department:
- _id: MaJö
- _id: PreCl
doi: 10.1038/s41593-025-01874-w
ec_funded: 1
external_id:
isi:
- '001416866800001'
pmid:
- '39930095'
fulldoi: https://doi.org/10.1038/s41593-025-01874-w
has_accepted_license: '1'
intvolume: ' 28'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41593-025-01874-w
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '756502'
name: Circuits of Visual Attention
- _id: bdaf81a8-d553-11ed-ba76-c95961984540
grant_number: '101086580'
name: 'Action Selection in the Midbrain: Neuromodulation of Visuomotor Senses'
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1098-2017
name: Connecting sensory with motor processing in the superior colliculus
- _id: 266D407A-B435-11E9-9278-68D0E5697425
grant_number: LT000256
name: Neuronal networks of salience and spatial detection in the murine superior
colliculus
publication: Nature Neuroscience
publication_identifier:
eissn:
- 1546-1726
issn:
- 1097-6256
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/high-tech-video-optimization-in-our-brain/
record:
- id: '18579'
relation: research_data
status: public
scopus_import: '1'
status: public
title: A thalamic hub-and-spoke network enables visual perception during action by
coordinating visuomotor dynamics
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: 28
year: '2025'
...
---
OA_place: publisher
_id: '19557'
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: ScienComp
acknowledgement: "The work presented in this doctoral thesis was performed at the
Institute of Science\r\nand Technology (ISTA) and financially supported by a European
Research Council\r\n(ERC) Consolidator Grant (PR1028ERC02), by SFARI (PR1028SIM02)
and by the\r\nAustrian Science Fund (FWF) to Gaia Novarino (PE1028W1232). I am very
thankful\r\nto the Doctoral Program “Molecular Drug Targets” (MolTag) for offering
me financial\r\nsupport to perform essential experiments during my PhD studies and
to participate in\r\ninternational conferences and courses."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
citation:
ama: Schwarz LA. Mapping developmental dynamics of autism spectrum disorder mouse
models at single-cell resolution. 2025. doi:10.15479/AT-ISTA-19557
apa: Schwarz, L. A. (2025). Mapping developmental dynamics of autism spectrum
disorder mouse models at single-cell resolution. Institute of Science and
Technology Austria. https://doi.org/10.15479/AT-ISTA-19557
chicago: Schwarz, Lena A. “Mapping Developmental Dynamics of Autism Spectrum Disorder
Mouse Models at Single-Cell Resolution.” Institute of Science and Technology Austria,
2025. https://doi.org/10.15479/AT-ISTA-19557.
ieee: L. A. Schwarz, “Mapping developmental dynamics of autism spectrum disorder
mouse models at single-cell resolution,” Institute of Science and Technology Austria,
2025.
ista: Schwarz LA. 2025. Mapping developmental dynamics of autism spectrum disorder
mouse models at single-cell resolution. Institute of Science and Technology Austria.
mla: Schwarz, Lena A. Mapping Developmental Dynamics of Autism Spectrum Disorder
Mouse Models at Single-Cell Resolution. Institute of Science and Technology
Austria, 2025, doi:10.15479/AT-ISTA-19557.
short: L.A. Schwarz, Mapping Developmental Dynamics of Autism Spectrum Disorder
Mouse Models at Single-Cell Resolution, Institute of Science and Technology Austria,
2025.
corr_author: '1'
date_created: 2025-04-14T06:59:06Z
date_published: 2025-04-14T00:00:00Z
date_updated: 2026-04-14T09:07:14Z
day: '14'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/AT-ISTA-19557
file:
- access_level: closed
checksum: 50290a8604edb0a720387f01e9d59fe4
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: lschwarz
date_created: 2025-04-15T08:43:36Z
date_updated: 2025-04-15T08:43:36Z
file_id: '19561'
file_name: Schwarz_Thesis_2025_FINAL.docx
file_size: 21783427
relation: source_file
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checksum: ed028488180ac4901e018ef1c330cf01
content_type: application/pdf
creator: lschwarz
date_created: 2025-04-15T08:43:42Z
date_updated: 2026-03-27T13:15:08Z
embargo: 2026-10-15
embargo_to: open_access
file_id: '19562'
file_name: Schwarz_Thesis_2025_FINALpdfa.pdf
file_size: 11432175
relation: main_file
file_date_updated: 2026-03-27T13:15:08Z
fulldoi: https://doi.org/10.15479/AT-ISTA-19557
has_accepted_license: '1'
language:
- iso: eng
month: '04'
oa_version: Published Version
page: '124'
project:
- _id: 9B91375C-BA93-11EA-9121-9846C619BF3A
grant_number: '707964'
name: Critical windows and reversibility of ASD associated with mutations in chromatin
remodelers
- _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: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '12802'
relation: part_of_dissertation
status: public
- id: '9429'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: Mapping developmental dynamics of autism spectrum disorder mouse models at
single-cell 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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
APC_amount: 2236,02 EUR
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '19566'
abstract:
- lang: eng
text: "Purpose: Optic nerve crush (ONC) is a model for studying optic nerve trauma.
Unilateral ONC induces massive retinal ganglion cell (RGC) degeneration in the
affected eye, leading to vision loss within a month. A common assumption has been
that the non-injured contralateral eye is unaffected due to the minimal retino-retinal
projections of the RGCs at the chiasm. Yet, recently, microglia, the brain-resident
macrophages, have shown a responsive phenotype in the contralateral eye after
ONC. Whether RGC loss accompanies this phenotype is still controversial.\r\n\r\nMethods:
Using the available RGCode algorithm and developing our own RGC-Quant deep-learning-based
tool, we quantify RGC's total number and density across the entire retina after
ONC.\r\n\r\nResults: We confirm a short-term microglia response in the contralateral
eye after ONC, but this did not affect the microglia number. Furthermore, we cannot
confirm the previously reported RGC loss between naïve and contralateral retinas
5 weeks after ONC induction across the commonly used Cx3cr1creERT2 and C57BL6/J
mouse models. Neither sex nor the direct comparison of the RGC markers Brn3a and
RBPMS, with Brn3a co-labeling, on average, 89% of the RBPMS+-cells, explained
this discrepancy, suggesting that the early microglia-responsive phenotype does
not have immediate consequences on the RGC number.\r\n\r\nConclusions: Our results
corroborate that unilateral optic nerve injury elicits a microglial response in
the uninjured contralateral eye but without RGC loss. Therefore, the contralateral
eye should be treated separately and not as an ONC control."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "The authors thank the Scientific Service Units (SSU) of ISTA for
the provided resources, specifically the Imaging and Optics Facility (IOF), the
Lab Support Facility (LSF), and the Pre-Clinical Facility (PCF) team, specifically
Sonja Haslinger, Claudia Gold, and Michael Schunn, for mouse colony management and
support. We thank all members of the Siegert group for constant feedback on the
project and the manuscript. \r\nSupported in whole or in part by the Austrian Science
Fund (FWF) [10.55776/P37131]. For open access purposes, the author has applied a
CC BY public copyright license to any author-accepted manuscript version arising
from this submission. "
article_number: '49'
article_processing_charge: Yes
article_type: original
author:
- first_name: Florianne E
full_name: Schoot Uiterkamp, Florianne E
id: 3526230C-F248-11E8-B48F-1D18A9856A87
last_name: Schoot Uiterkamp
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Mohammad
full_name: Alamalhoda, Mohammad
last_name: Alamalhoda
- first_name: Arsalan
full_name: Firoozi, Arsalan
last_name: Firoozi
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. Optic nerve
crush does not induce retinal ganglion cell loss in the contralateral eye. Investigative
Ophthalmology & Visual Science. 2025;66(3). doi:10.1167/iovs.66.3.49
apa: Miteva, F. E., Maes, M. E., Alamalhoda, M., Firoozi, A., Colombo, G., &
Siegert, S. (2025). Optic nerve crush does not induce retinal ganglion cell loss
in the contralateral eye. Investigative Ophthalmology & Visual Science.
Association for Research in Vision and Ophthalmology. https://doi.org/10.1167/iovs.66.3.49
chicago: Miteva, Florianne E, Margaret E Maes, Mohammad Alamalhoda, Arsalan Firoozi,
Gloria Colombo, and Sandra Siegert. “Optic Nerve Crush Does Not Induce Retinal
Ganglion Cell Loss in the Contralateral Eye.” Investigative Ophthalmology &
Visual Science. Association for Research in Vision and Ophthalmology, 2025.
https://doi.org/10.1167/iovs.66.3.49.
ieee: F. E. Miteva, M. E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, and S. Siegert,
“Optic nerve crush does not induce retinal ganglion cell loss in the contralateral
eye,” Investigative Ophthalmology & Visual Science, vol. 66, no. 3.
Association for Research in Vision and Ophthalmology, 2025.
ista: Miteva FE, Maes ME, Alamalhoda M, Firoozi A, Colombo G, Siegert S. 2025. Optic
nerve crush does not induce retinal ganglion cell loss in the contralateral eye.
Investigative Ophthalmology & Visual Science. 66(3), 49.
mla: Miteva, Florianne E., et al. “Optic Nerve Crush Does Not Induce Retinal Ganglion
Cell Loss in the Contralateral Eye.” Investigative Ophthalmology & Visual
Science, vol. 66, no. 3, 49, Association for Research in Vision and Ophthalmology,
2025, doi:10.1167/iovs.66.3.49.
short: F.E. Miteva, M.E. Maes, M. Alamalhoda, A. Firoozi, G. Colombo, S. Siegert,
Investigative Ophthalmology & Visual Science 66 (2025).
corr_author: '1'
date_created: 2025-04-15T13:40:35Z
date_published: 2025-03-01T00:00:00Z
date_updated: 2026-05-20T06:37:12Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
doi: 10.1167/iovs.66.3.49
external_id:
pmid:
- '40126507'
file:
- access_level: open_access
checksum: e8722ce5792f6c08fe1e191f7de6f147
content_type: application/pdf
creator: dernst
date_created: 2025-04-15T13:49:10Z
date_updated: 2025-04-15T13:49:10Z
file_id: '19567'
file_name: 2025_IOVS_SchootUiterkamp.pdf
file_size: 2721477
relation: main_file
success: 1
file_date_updated: 2025-04-15T13:49:10Z
fulldoi: https://doi.org/10.1167/iovs.66.3.49
has_accepted_license: '1'
intvolume: ' 66'
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 7be82147-9f16-11ee-852c-f44682d73140
grant_number: P37131
name: Dissecting the morpho-functional relationship of microglia
- _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1
call_identifier: FWF
name: FWF Open Access Fund
publication: Investigative Ophthalmology & Visual Science
publication_identifier:
issn:
- 1552-5783
publication_status: published
publisher: Association for Research in Vision and Ophthalmology
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/siegert-lab/RGC-Quant
record:
- id: '20467'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Optic nerve crush does not induce retinal ganglion cell loss in the contralateral
eye
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: 66
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. Nature. 2025;642:398-410. doi:10.1038/s41586-025-08985-1
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. Nature. Springer Nature. https://doi.org/10.1038/s41586-025-08985-1
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.” Nature. Springer
Nature, 2025. https://doi.org/10.1038/s41586-025-08985-1.
ieee: M. Tavakoli et al., “Light-microscopy-based connectomic reconstruction
of mammalian brain tissue,” Nature, 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.” Nature, vol. 642, Springer Nature, 2025, pp.
398–410, doi:10.1038/s41586-025-08985-1.
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: 2026-04-28T13:33:34Z
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: '18677'
relation: earlier_version
status: public
- id: '18697'
relation: research_data
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'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20099'
abstract:
- lang: eng
text: The hippocampus, critical for learning and memory, is dogmatically described
as a trisynaptic circuit where dentate gyrus granule cells (GCs), CA3 pyramidal
neurons (PNs), and CA1 PNs are serially connected. However, CA3 also forms an
autoassociative network, and its PNs have diverse morphologies, intrinsic properties,
and GC input levels. How PN subtypes compose this recurrent network is unknown.
To determine the synaptic arrangement of identified CA3 PNs, we combine multicellular
patch-clamp recording and post hoc morphological analysis in mouse hippocampal
slices. PNs can be divided into distinct “superficial” and “deep” subclasses,
the latter including previously reported “athorny” cells. Subclasses have distinct
input-output transformations and asymmetric connectivity, which is more abundant
from superficial to deep PNs, splitting CA3 locally into two parallel recurrent
networks. Coincident spontaneous inhibition occurs frequently within but not between
subclasses, implying subclass-specific inhibitory innervation. Our results suggest
two separately controlled sublayers for parallel information processing in hippocampal
CA3.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
acknowledgement: We thank Andrea Navas-Olive and Rebecca J. Morse-Mora for critically
reading an earlier version of the manuscript. We also thank Florian Marr and Christina
Altmutter for excellent technical assistance, Alois Schlögl for programming and
data-handling assistance, Todor Asenov for technical support, and Eleftheria Kralli-Beller
for manuscript editing. This research was supported by the Scientific Services Units
(SSUs) of ISTA. We are particularly grateful for assistance from the Imaging and
Optics Facility, Preclinical Facility, Lab Support Facility, and Miba Machine Shop.
The project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation program (grant agreement no.
692692 to P.J., Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635
to J.F.W., and an ISTplus Fellowship through Marie Skłodowska-Curie grant agreement
no. 754411 to V.V.-B.), the Austrian Science Fund (P 36232-B, PAT 4178023, and Cluster
of Excellence 10.55776/COE16 to P.J.), and a CONACyT fellowship (289638 to V.V.-B.)
and was supported by a non-stipendiary EMBO fellowship (ALTF 756–2020 to J.F.W.).
article_number: '116080'
article_processing_charge: Yes
article_type: original
author:
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Watson J, Vargas Barroso VM, Jonas PM. Cell-specific wiring routes information
flow through hippocampal CA3. Cell Reports. 2025;44(8). doi:10.1016/j.celrep.2025.116080
apa: Watson, J., Vargas Barroso, V. M., & Jonas, P. M. (2025). Cell-specific
wiring routes information flow through hippocampal CA3. Cell Reports. Elsevier.
https://doi.org/10.1016/j.celrep.2025.116080
chicago: Watson, Jake, Victor M Vargas Barroso, and Peter M Jonas. “Cell-Specific
Wiring Routes Information Flow through Hippocampal CA3.” Cell Reports.
Elsevier, 2025. https://doi.org/10.1016/j.celrep.2025.116080.
ieee: J. Watson, V. M. Vargas Barroso, and P. M. Jonas, “Cell-specific wiring routes
information flow through hippocampal CA3,” Cell Reports, vol. 44, no. 8.
Elsevier, 2025.
ista: Watson J, Vargas Barroso VM, Jonas PM. 2025. Cell-specific wiring routes information
flow through hippocampal CA3. Cell Reports. 44(8), 116080.
mla: Watson, Jake, et al. “Cell-Specific Wiring Routes Information Flow through
Hippocampal CA3.” Cell Reports, vol. 44, no. 8, 116080, Elsevier, 2025,
doi:10.1016/j.celrep.2025.116080.
short: J. Watson, V.M. Vargas Barroso, P.M. Jonas, Cell Reports 44 (2025).
corr_author: '1'
date_created: 2025-08-03T22:01:30Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2025-09-30T14:12:02Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.celrep.2025.116080
ec_funded: 1
external_id:
isi:
- '001544472300002'
file:
- access_level: open_access
checksum: 556ff9760661ecd23949d75031043b1f
content_type: application/pdf
creator: dernst
date_created: 2025-08-04T06:53:07Z
date_updated: 2025-08-04T06:53:07Z
file_id: '20106'
file_name: 2025_CellReports_Watson.pdf
file_size: 27695214
relation: main_file
success: 1
file_date_updated: 2025-08-04T06:53:07Z
fulldoi: https://doi.org/10.1016/j.celrep.2025.116080
has_accepted_license: '1'
intvolume: ' 44'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _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: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Cell Reports
publication_identifier:
eissn:
- 2211-1247
issn:
- 2639-1856
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cell-specific wiring routes information flow through hippocampal CA3
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 44
year: '2025'
...
---
APC_amount: 5766,07 EUR
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20289'
abstract:
- lang: eng
text: Cell and tissue movement in development, cancer invasion, and immune response
relies on chemical or mechanical guidance cues. In many systems, this behavior
is locally directed by self-generated signaling gradients rather than long-range,
prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally
and navigate through self-generated gradients remains largely unexplored. Here,
we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous
cell populations. We find that the relative chemotactic sensitivities of different
cell populations control their long-time coupling and comigration dynamics, with
boundary conditions such as external cell and attractant reservoirs substantially
influencing the migration patterns. Our model predicts an optimal parameter regime
that enables robust and colocalized migration. We test our theoretical predictions
with in vitro experiments demonstrating the comigration of distinct immune cell
populations, and quantitatively reproduce observed migration patterns under wild-type
and perturbed conditions. Interestingly, immune cell comigration occurs close
to the predicted optimal regime. Finally, we incorporate mechanical interactions
into our framework, revealing a nontrivial interplay between chemotactic and mechanical
nonreciprocity in driving collective migration. Together, our findings suggest
that self-generated chemotaxis is a robust strategy for the navigation of mixed
cell populations.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: NanoFab
acknowledgement: We thank all members of the M.S. and E.H. groups for stimulating
discussions.We thank the Imaging and Optics facility, the Pre-clinical and Lab Support
facility of the Institute of Science and Technology Austria for their excellent
support and provided resources for the experimental research. In particular, we
thank Jack Merrin from the Nanofabrication facility who generated the microfabricated
channel used in this study. This work received funding fromt he European Research
Council under the European Union’s Horizon 2020 research and innovation program
(grant agreement No. 851288 to E.H.). M.C.U.is funded by a University of Sheffield
Strategic Research Fellowship in the Physics of Life and Quantitative Biology.
article_number: e2504064122
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Mehmet C
full_name: Ucar, Mehmet C
id: 50B2A802-6007-11E9-A42B-EB23E6697425
last_name: Ucar
orcid: 0000-0003-0506-4217
- first_name: Alsberga
full_name: Zane, Alsberga
id: 60f7509a-f652-11ea-9d86-b963d6490d7c
last_name: Zane
orcid: 0009-0003-0415-7603
- first_name: Jonna H
full_name: Alanko, Jonna H
id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
last_name: Alanko
orcid: 0000-0002-7698-3061
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. Self-generated chemotaxis
of mixed cell populations. Proceedings of the National Academy of Sciences.
2025;122(34). doi:10.1073/pnas.2504064122
apa: Ucar, M. C., Zane, A., Alanko, J. H., Sixt, M. K., & Hannezo, E. B. (2025).
Self-generated chemotaxis of mixed cell populations. Proceedings of the National
Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.2504064122
chicago: Ucar, Mehmet C, Alsberga Zane, Jonna H Alanko, Michael K Sixt, and Edouard
B Hannezo. “Self-Generated Chemotaxis of Mixed Cell Populations.” Proceedings
of the National Academy of Sciences. National Academy of Sciences, 2025. https://doi.org/10.1073/pnas.2504064122.
ieee: M. C. Ucar, A. Zane, J. H. Alanko, M. K. Sixt, and E. B. Hannezo, “Self-generated
chemotaxis of mixed cell populations,” Proceedings of the National Academy
of Sciences, vol. 122, no. 34. National Academy of Sciences, 2025.
ista: Ucar MC, Zane A, Alanko JH, Sixt MK, Hannezo EB. 2025. Self-generated chemotaxis
of mixed cell populations. Proceedings of the National Academy of Sciences. 122(34),
e2504064122.
mla: Ucar, Mehmet C., et al. “Self-Generated Chemotaxis of Mixed Cell Populations.”
Proceedings of the National Academy of Sciences, vol. 122, no. 34, e2504064122,
National Academy of Sciences, 2025, doi:10.1073/pnas.2504064122.
short: M.C. Ucar, A. Zane, J.H. Alanko, M.K. Sixt, E.B. Hannezo, Proceedings of
the National Academy of Sciences 122 (2025).
corr_author: '1'
date_created: 2025-09-07T22:01:32Z
date_published: 2025-08-26T00:00:00Z
date_updated: 2026-05-20T08:59:54Z
day: '26'
ddc:
- '570'
department:
- _id: EdHa
- _id: MiSi
doi: 10.1073/pnas.2504064122
ec_funded: 1
external_id:
isi:
- '001562181600001'
pmid:
- '40838890'
file:
- access_level: open_access
checksum: b36abd92673b6d76376fc9434bad52cc
content_type: application/pdf
creator: dernst
date_created: 2025-09-08T07:23:29Z
date_updated: 2025-09-08T07:23:29Z
file_id: '20307'
file_name: 2025_PNAS_Ucar.pdf
file_size: 16069140
relation: main_file
success: 1
file_date_updated: 2025-09-08T07:23:29Z
fulldoi: https://doi.org/10.1073/pnas.2504064122
has_accepted_license: '1'
intvolume: ' 122'
isi: 1
issue: '34'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/mehmetcanucar/Self-generated-chemotaxis
scopus_import: '1'
status: public
title: Self-generated chemotaxis of mixed cell populations
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: 122
year: '2025'
...