---
_id: '12679'
abstract:
- lang: eng
text: How to generate a brain of correct size and with appropriate cell-type diversity
during development is a major question in Neuroscience. In the developing neocortex,
radial glial progenitor (RGP) cells are the main neural stem cells that produce
cortical excitatory projection neurons, glial cells, and establish the prospective
postnatal stem cell niche in the lateral ventricles. RGPs follow a tightly orchestrated
developmental program that when disrupted can result in severe cortical malformations
such as microcephaly and megalencephaly. The precise cellular and molecular mechanisms
instructing faithful RGP lineage progression are however not well understood.
This review will summarize recent conceptual advances that contribute to our understanding
of the general principles of RGP lineage progression.
acknowledgement: "I wish to thank all current and past members of the Hippenmeyer
laboratory at ISTA for exciting discussions on the subject of this review. I apologize
to colleagues whose work I could not cite and/or discuss in the frame of the available
space. Work in the Hippenmeyer laboratory on the\r\ndiscussed topic is supported
by ISTA institutional funds, FWF SFB F78 to S.H., and the European Research Council
(ERC) under the European Union’s Horizon 2020 Research and Innovation Programme
(grant agree-ment no. 725780 LinPro) to SH."
article_number: '102695'
article_processing_charge: Yes (via OA deal)
article_type: review
author:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: 'Hippenmeyer S. Principles of neural stem cell lineage progression: Insights
from developing cerebral cortex. Current Opinion in Neurobiology. 2023;79(4).
doi:10.1016/j.conb.2023.102695'
apa: 'Hippenmeyer, S. (2023). Principles of neural stem cell lineage progression:
Insights from developing cerebral cortex. Current Opinion in Neurobiology.
Elsevier. https://doi.org/10.1016/j.conb.2023.102695'
chicago: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression:
Insights from Developing Cerebral Cortex.” Current Opinion in Neurobiology.
Elsevier, 2023. https://doi.org/10.1016/j.conb.2023.102695.'
ieee: 'S. Hippenmeyer, “Principles of neural stem cell lineage progression: Insights
from developing cerebral cortex,” Current Opinion in Neurobiology, vol.
79, no. 4. Elsevier, 2023.'
ista: 'Hippenmeyer S. 2023. Principles of neural stem cell lineage progression:
Insights from developing cerebral cortex. Current Opinion in Neurobiology. 79(4),
102695.'
mla: 'Hippenmeyer, Simon. “Principles of Neural Stem Cell Lineage Progression: Insights
from Developing Cerebral Cortex.” Current Opinion in Neurobiology, vol.
79, no. 4, 102695, Elsevier, 2023, doi:10.1016/j.conb.2023.102695.'
short: S. Hippenmeyer, Current Opinion in Neurobiology 79 (2023).
corr_author: '1'
date_created: 2023-02-26T12:24:21Z
date_published: 2023-04-01T00:00:00Z
date_updated: 2025-04-15T08:23:06Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.conb.2023.102695
ec_funded: 1
external_id:
isi:
- '000953497700001'
pmid:
- '36842274'
file:
- access_level: open_access
checksum: 4d11c4ca87e6cbc4d2ac46d3225ea615
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T12:29:06Z
date_updated: 2023-08-16T12:29:06Z
file_id: '14071'
file_name: 2023_CurrentOpinionNeurobio_Hippenmeyer.pdf
file_size: 1787894
relation: main_file
success: 1
file_date_updated: 2023-08-16T12:29:06Z
has_accepted_license: '1'
intvolume: ' 79'
isi: 1
issue: '4'
keyword:
- General Neuroscience
language:
- iso: eng
month: '04'
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: Current Opinion in Neurobiology
publication_identifier:
issn:
- 0959-4388
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Principles of neural stem cell lineage progression: Insights from developing
cerebral cortex'
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: 79
year: '2023'
...
---
_id: '12802'
abstract:
- lang: eng
text: Little is known about the critical metabolic changes that neural cells have
to undergo during development and how temporary shifts in this program can influence
brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5,
a transporter of metabolically essential large neutral amino acids (LNAAs), lead
to autism, we employed metabolomic profiling to study the metabolic states of
the cerebral cortex across different developmental stages. We found that the forebrain
undergoes significant metabolic remodeling throughout development, with certain
groups of metabolites showing stage-specific changes, but what are the consequences
of perturbing this metabolic program? By manipulating Slc7a5 expression in neural
cells, we found that the metabolism of LNAAs and lipids are interconnected in
the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state,
leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific
alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Freeman and V. Voronin for technical assistance, S. Deixler,
A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal
colony. We thank L. Andersen and J. Sonntag, who were involved in generating the
MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance
with the proteomic analysis, as well as the ISTA electron microscopy and Imaging
and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed
by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge
the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular
metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was
performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated
using Biorender.com. This work was supported by the Austrian Science Fund (FWF,
DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Daniel
full_name: Malzl, Daniel
last_name: Malzl
- first_name: Maria
full_name: Gerykova Bujalkova, Maria
last_name: Gerykova Bujalkova
- first_name: Mateja
full_name: Smogavec, Mateja
last_name: Smogavec
- first_name: Lena A.
full_name: Schwarz, Lena A.
last_name: Schwarz
- first_name: Sarah
full_name: Gorkiewicz, Sarah
id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
last_name: Gorkiewicz
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Christian
full_name: Knittl-Frank, Christian
last_name: Knittl-Frank
- first_name: Marianna
full_name: Tassinari, Marianna
id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e
last_name: Tassinari
- first_name: Nuno
full_name: Maulide, Nuno
last_name: Maulide
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal
neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037
apa: Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz,
L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal
excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037
chicago: Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova,
Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino
Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier,
2023. https://doi.org/10.1016/j.cell.2023.02.037.
ieee: L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal
excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25,
2023.
ista: Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA,
Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke
T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels
tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.
mla: Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal
Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25,
doi:10.1016/j.cell.2023.02.037.
short: L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A.
Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N.
Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.
corr_author: '1'
date_created: 2023-04-05T08:15:40Z
date_published: 2023-04-27T00:00:00Z
date_updated: 2026-04-14T08:34:36Z
day: '27'
ddc:
- '570'
department:
- _id: SiHi
- _id: GaNo
doi: 10.1016/j.cell.2023.02.037
ec_funded: 1
external_id:
isi:
- '000991468700001'
pmid:
- '36996814'
file:
- access_level: open_access
checksum: 47e94fbe19e86505b429cb7a5b503ce6
content_type: application/pdf
creator: dernst
date_created: 2023-05-02T09:26:21Z
date_updated: 2023-05-02T09:26:21Z
file_id: '12889'
file_name: 2023_Cell_Knaus.pdf
file_size: 15712841
relation: main_file
success: 1
file_date_updated: 2023-05-02T09:26:21Z
has_accepted_license: '1'
intvolume: ' 186'
isi: 1
issue: '9'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1950-1967.e25
pmid: 1
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
publication: Cell
publication_identifier:
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/feed-them-or-lose-them/
record:
- id: '19557'
relation: dissertation_contains
status: public
- id: '13107'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Large neutral amino acid levels tune perinatal neuronal excitability and survival
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: 186
year: '2023'
...
---
_id: '14757'
abstract:
- lang: eng
text: The cerebral cortex is comprised of a vast cell-type diversity sequentially
generated by cortical progenitor cells. Faithful progenitor lineage progression
requires the tight orchestration of distinct molecular and cellular mechanisms
regulating proper progenitor proliferation behavior and differentiation. Correct
execution of developmental programs involves a complex interplay of cell intrinsic
and tissue-wide mechanisms. Many studies over the past decades have been able
to determine a plethora of genes critically involved in cortical development.
However, only a few made use of genetic paradigms with sparse and global gene
deletion to probe cell-autonomous vs. tissue-wide contribution. In this chapter,
we will elaborate on the importance of dissecting the cell-autonomous and tissue-wide
mechanisms to gain a precise understanding of gene function during radial glial
progenitor lineage progression.
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: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- 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, Amberg N, Hippenmeyer S. Interplay of Cell‐autonomous
Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage
Progression. In: Huttner W, ed. Neocortical Neurogenesis in Development and
Evolution. Wiley; 2023:169-191. doi:10.1002/9781119860914.ch10'
apa: Villalba Requena, A., Amberg, N., & Hippenmeyer, S. (2023). Interplay of
Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial
Progenitor Lineage Progression. In W. Huttner (Ed.), Neocortical Neurogenesis
in Development and Evolution (pp. 169–191). Wiley. https://doi.org/10.1002/9781119860914.ch10
chicago: Villalba Requena, Ana, Nicole Amberg, and Simon Hippenmeyer. “Interplay
of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating Radial
Glial Progenitor Lineage Progression.” In Neocortical Neurogenesis in Development
and Evolution, edited by Wieland Huttner, 169–91. Wiley, 2023. https://doi.org/10.1002/9781119860914.ch10.
ieee: A. Villalba Requena, N. Amberg, and S. Hippenmeyer, “Interplay of Cell‐autonomous
Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage
Progression,” in Neocortical Neurogenesis in Development and Evolution,
W. Huttner, Ed. Wiley, 2023, pp. 169–191.
ista: 'Villalba Requena A, Amberg N, Hippenmeyer S. 2023.Interplay of Cell‐autonomous
Gene Function and Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage
Progression. In: Neocortical Neurogenesis in Development and Evolution. , 169–191.'
mla: Villalba Requena, Ana, et al. “Interplay of Cell‐autonomous Gene Function and
Tissue‐wide Mechanisms Regulating Radial Glial Progenitor Lineage Progression.”
Neocortical Neurogenesis in Development and Evolution, edited by Wieland
Huttner, Wiley, 2023, pp. 169–91, doi:10.1002/9781119860914.ch10.
short: A. Villalba Requena, N. Amberg, S. Hippenmeyer, in:, W. Huttner (Ed.), Neocortical
Neurogenesis in Development and Evolution, Wiley, 2023, pp. 169–191.
corr_author: '1'
date_created: 2024-01-08T13:16:36Z
date_published: 2023-08-08T00:00:00Z
date_updated: 2024-10-09T21:07:46Z
day: '08'
department:
- _id: SiHi
doi: 10.1002/9781119860914.ch10
editor:
- first_name: Wieland
full_name: Huttner, Wieland
last_name: Huttner
language:
- iso: eng
month: '08'
oa_version: None
page: 169-191
publication: Neocortical Neurogenesis in Development and Evolution
publication_identifier:
eisbn:
- '9781119860914'
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Interplay of Cell‐autonomous Gene Function and Tissue‐wide Mechanisms Regulating
Radial Glial Progenitor Lineage Progression
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '14783'
abstract:
- lang: eng
text: Connexin 43, an astroglial gap junction protein, is enriched in perisynaptic
astroglial processes and plays major roles in synaptic transmission. We have previously
found that astroglial Cx43 controls synaptic glutamate levels and allows for activity-dependent
glutamine release to sustain physiological synaptic transmissions and cognitiogns.
However, whether Cx43 is important for the release of synaptic vesicles, which
is a critical component of synaptic efficacy, remains unanswered. Here, using
transgenic mice with a glial conditional knockout of Cx43 (Cx43−/−), we investigate
whether and how astrocytes regulate the release of synaptic vesicles from hippocampal
synapses. We report that CA1 pyramidal neurons and their synapses develop normally
in the absence of astroglial Cx43. However, a significant impairment in synaptic
vesicle distribution and release dynamics were observed. In particular, the FM1-43
assays performed using two-photon live imaging and combined with multi-electrode
array stimulation in acute hippocampal slices, revealed a slower rate of synaptic
vesicle release in Cx43−/− mice. Furthermore, paired-pulse recordings showed that
synaptic vesicle release probability was also reduced and is dependent on glutamine
supply via Cx43 hemichannel (HC). Taken together, we have uncovered a role for
Cx43 in regulating presynaptic functions by controlling the rate and probability
of synaptic vesicle release. Our findings further highlight the significance of
astroglial Cx43 in synaptic transmission and efficacy.
acknowledgement: 'This research was funded by grants from the European Research Council
(Consolidator grant #683154) and European Union’s Horizon 2020 research and innovation
program (Marie Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD)
to N.R., as well as from FP7-PEOPLE Marie Curie Intra-European Fellowship for career
development (grant #622289) to G.C. We thank Elena Dossi, Grégory Ghézali, and Jérémie
Teillon for support with setting up the MEA system for the two-photon microscope.
We would also like to thank Tayfun Palaz for their technical assistance with the
EM preparations.'
article_number: '1133'
article_processing_charge: Yes
article_type: original
author:
- 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: Oana
full_name: Chever, Oana
last_name: Chever
- first_name: Astrid
full_name: Rollenhagen, Astrid
last_name: Rollenhagen
- first_name: Nicole
full_name: Quenech’du, Nicole
last_name: Quenech’du
- first_name: Pascal
full_name: Ezan, Pascal
last_name: Ezan
- first_name: Joachim H. R.
full_name: Lübke, Joachim H. R.
last_name: Lübke
- first_name: Nathalie
full_name: Rouach, Nathalie
last_name: Rouach
citation:
ama: Cheung GT, Chever O, Rollenhagen A, et al. Astroglial connexin 43 regulates
synaptic vesicle release at hippocampal synapses. Cells. 2023;12(8). doi:10.3390/cells12081133
apa: Cheung, G. T., Chever, O., Rollenhagen, A., Quenech’du, N., Ezan, P., Lübke,
J. H. R., & Rouach, N. (2023). Astroglial connexin 43 regulates synaptic vesicle
release at hippocampal synapses. Cells. MDPI. https://doi.org/10.3390/cells12081133
chicago: Cheung, Giselle T, Oana Chever, Astrid Rollenhagen, Nicole Quenech’du,
Pascal Ezan, Joachim H. R. Lübke, and Nathalie Rouach. “Astroglial Connexin 43
Regulates Synaptic Vesicle Release at Hippocampal Synapses.” Cells. MDPI,
2023. https://doi.org/10.3390/cells12081133.
ieee: G. T. Cheung et al., “Astroglial connexin 43 regulates synaptic vesicle
release at hippocampal synapses,” Cells, vol. 12, no. 8. MDPI, 2023.
ista: Cheung GT, Chever O, Rollenhagen A, Quenech’du N, Ezan P, Lübke JHR, Rouach
N. 2023. Astroglial connexin 43 regulates synaptic vesicle release at hippocampal
synapses. Cells. 12(8), 1133.
mla: Cheung, Giselle T., et al. “Astroglial Connexin 43 Regulates Synaptic Vesicle
Release at Hippocampal Synapses.” Cells, vol. 12, no. 8, 1133, MDPI, 2023,
doi:10.3390/cells12081133.
short: G.T. Cheung, O. Chever, A. Rollenhagen, N. Quenech’du, P. Ezan, J.H.R. Lübke,
N. Rouach, Cells 12 (2023).
date_created: 2024-01-10T09:46:35Z
date_published: 2023-04-11T00:00:00Z
date_updated: 2024-01-16T09:29:35Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3390/cells12081133
external_id:
isi:
- '000977445700001'
pmid:
- '37190042'
file:
- access_level: open_access
checksum: 6798cd75d8857976fbc58a43fd173d68
content_type: application/pdf
creator: dernst
date_created: 2024-01-16T09:26:52Z
date_updated: 2024-01-16T09:26:52Z
file_id: '14808'
file_name: 2023_Cells_Cheung.pdf
file_size: 7931643
relation: main_file
success: 1
file_date_updated: 2024-01-16T09:26:52Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '8'
keyword:
- General Medicine
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Cells
publication_identifier:
issn:
- 2073-4409
publication_status: published
publisher: MDPI
quality_controlled: '1'
status: public
title: Astroglial connexin 43 regulates synaptic vesicle release at hippocampal synapses
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: 12
year: '2023'
...
---
_id: '11336'
abstract:
- lang: eng
text: The generation of a correctly-sized cerebral cortex with all-embracing neuronal
and glial cell-type diversity critically depends on faithful radial glial progenitor
(RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression
is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity
results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene
expression instructs RGP lineage progression is unknown. Here we utilize Mosaic
Analysis with Double Markers (MADM)-based single cell technology and demonstrate
that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts
at the global tissue-wide level. Conversely, cortical astrocyte production and
maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation.
We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression
that are dependent on complex interplays between intrinsic and tissue-wide properties.
In a broader context our results imply a critical role for the genetic and cellular
niche environment in neural stem cell behavior.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit) and S. Gharagozlou for technical support. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics
Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A.
received funding from the FWF Firnberg-Programm (T 1031). The work was supported by IST institutional funds 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.
article_number: abq1263
article_processing_charge: No
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- 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: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular
landscape shapes the execution of sequential PRC2 functions in neural stem cell
lineage progression. Science Advances. 2022;8(44). doi:10.1126/sciadv.abq1263
apa: Amberg, N., Pauler, F., Streicher, C., & Hippenmeyer, S. (2022). Tissue-wide
genetic and cellular landscape shapes the execution of sequential PRC2 functions
in neural stem cell lineage progression. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.abq1263
chicago: Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer.
“Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential
PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances.
American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abq1263.
ieee: N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression,” Science Advances, vol. 8, no. 44. American
Association for the Advancement of Science, 2022.
ista: Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression. Science Advances. 8(44), abq1263.
mla: Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the
Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.”
Science Advances, vol. 8, no. 44, abq1263, American Association for the
Advancement of Science, 2022, doi:10.1126/sciadv.abq1263.
short: N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).
corr_author: '1'
date_created: 2022-04-26T15:04:50Z
date_published: 2022-11-01T00:00:00Z
date_updated: 2025-09-09T14:30:38Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.abq1263
ec_funded: 1
external_id:
isi:
- '000918406800019'
pmid:
- '36322669'
file:
- access_level: open_access
checksum: 0117023e188542082ca6693cf39e7f03
content_type: application/pdf
creator: patrickd
date_created: 2023-03-21T14:18:10Z
date_updated: 2023-03-21T14:18:10Z
file_id: '12742'
file_name: sciadv.abq1263.pdf
file_size: 2973998
relation: main_file
success: 1
file_date_updated: 2023-03-21T14:18:10Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
issue: '44'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/
scopus_import: '1'
status: public
title: Tissue-wide genetic and cellular landscape shapes the execution of sequential
PRC2 functions in neural stem cell lineage progression
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: 8
year: '2022'
...
---
_id: '11449'
abstract:
- lang: eng
text: Mutations are acquired frequently, such that each cell's genome inscribes
its history of cell divisions. Common genomic alterations involve loss of heterozygosity
(LOH). LOH accumulates throughout the genome, offering large encoding capacity
for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq)
of mouse brain cells, we found that LOH events spanning multiple genes are revealed
as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide
variants (SNVs). We simultaneously inferred cell lineage and marked developmental
time points based on X chromosome inactivation and the total number of LOH events
while identifying cell types from gene expression patterns. Our results are consistent
with progenitor cells giving rise to multiple cortical cell types through stereotyped
expansion and distinct waves of neurogenesis. This type of retrospective analysis
could be incorporated into scRNA-seq pipelines and, compared with experimental
approaches for determining lineage in model organisms, is applicable where genetic
engineering is prohibited, such as humans.
acknowledgement: D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk
Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory
to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University
of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b]
life science call grant (C13-002) and the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation program 725780 LinPro
to S.H.
article_processing_charge: No
article_type: original
author:
- first_name: Donovan J.
full_name: Anderson, Donovan J.
last_name: Anderson
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Aaron
full_name: Mckenna, Aaron
last_name: Mckenna
- first_name: Jay
full_name: Shendure, Jay
last_name: Shendure
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Marshall S.
full_name: Horwitz, Marshall S.
last_name: Horwitz
citation:
ama: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous
brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical
development. Cell Systems. 2022;13(6):438-453.e5. doi:10.1016/j.cels.2022.03.006
apa: Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., &
Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by
scRNA-seq reveals stereotyped cortical development. Cell Systems. Elsevier.
https://doi.org/10.1016/j.cels.2022.03.006
chicago: Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon
Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage
Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems.
Elsevier, 2022. https://doi.org/10.1016/j.cels.2022.03.006.
ieee: D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M.
S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq
reveals stereotyped cortical development,” Cell Systems, vol. 13, no. 6.
Elsevier, p. 438–453.e5, 2022.
ista: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022.
Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped
cortical development. Cell Systems. 13(6), 438–453.e5.
mla: Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined
by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems, vol.
13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:10.1016/j.cels.2022.03.006.
short: D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz,
Cell Systems 13 (2022) 438–453.e5.
date_created: 2022-06-19T22:01:57Z
date_published: 2022-06-15T00:00:00Z
date_updated: 2026-06-18T17:15:22Z
day: '15'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.cels.2022.03.006
ec_funded: 1
external_id:
isi:
- '000814124400002'
pmid:
- '35452605'
intvolume: ' 13'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cels.2022.03.006
month: '06'
oa: 1
oa_version: Published Version
page: 438-453.e5
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Cell Systems
publication_identifier:
eissn:
- 2405-4720
issn:
- 2405-4712
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped
cortical development
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2022'
...
---
_id: '11460'
abstract:
- lang: eng
text: "Background: Proper cerebral cortical development depends on the tightly orchestrated
migration of newly born neurons from the inner ventricular and subventricular
zones to the outer cortical plate. Any disturbance in this process during prenatal
stages may lead to neuronal migration disorders (NMDs), which can vary in extent
from focal to global. Furthermore, NMDs show a substantial comorbidity with other
neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous
work demonstrated focal neuronal migration defects in mice carrying loss-of-function
alleles of the recognized autism risk gene WDFY3. However, the cellular origins
of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide
critical insight into WDFY3-dependent disease pathology.\r\nMethods: Here, in
an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic
analysis with double markers (MADM). MADM technology enabled us to genetically
distinctly track and phenotypically analyze mutant and wild-type cells concomitantly
in vivo using immunofluorescent techniques.\r\nResults: We revealed a cell autonomous
requirement of WDFY3 for accurate laminar positioning of cortical projection neurons
and elimination of mispositioned cells during early postnatal life. In addition,
we identified significant deviations in dendritic arborization, as well as synaptic
density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant
neurons in Wdfy3-MADM reporter mice at postnatal stages.\r\nLimitations: While
Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD
pathology that remain inaccessible to investigation in humans, like most animal
models, they do not a perfectly replicate all aspects of human ASD biology. The
lack of human data makes it indeterminate whether morphological deviations described
here apply to ASD patients or some of the other neurodevelopmental conditions
associated with WDFY3 mutation.\r\nConclusions: Our genetic approach revealed
several cell autonomous requirements of WDFY3 in neuronal development that could
underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions.
The results are also consistent with findings in other ASD animal models and patients
and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity
in postnatal life."
acknowledgement: "This study was funded by NIMH R21MH115347 to KSZ. KSZ is further
supported by Shriners Hospitals for Children.\r\nWe would like to thank Angelo Harlan
de Crescenzo for early contributions to this project."
article_number: '27'
article_processing_charge: No
article_type: original
author:
- first_name: Zachary A.
full_name: Schaaf, Zachary A.
last_name: Schaaf
- first_name: Lyvin
full_name: Tat, Lyvin
last_name: Tat
- first_name: Noemi
full_name: Cannizzaro, Noemi
last_name: Cannizzaro
- first_name: Ralph
full_name: Green, Ralph
last_name: Green
- 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
- first_name: Konstantinos S.
full_name: Zarbalis, Konstantinos S.
last_name: Zarbalis
citation:
ama: Schaaf ZA, Tat L, Cannizzaro N, et al. WDFY3 mutation alters laminar position
and morphology of cortical neurons. Molecular Autism. 2022;13. doi:10.1186/s13229-022-00508-3
apa: Schaaf, Z. A., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer,
S., & Zarbalis, K. S. (2022). WDFY3 mutation alters laminar position and morphology
of cortical neurons. Molecular Autism. Springer Nature. https://doi.org/10.1186/s13229-022-00508-3
chicago: Schaaf, Zachary A., Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke,
Simon Hippenmeyer, and Konstantinos S. Zarbalis. “WDFY3 Mutation Alters Laminar
Position and Morphology of Cortical Neurons.” Molecular Autism. Springer
Nature, 2022. https://doi.org/10.1186/s13229-022-00508-3.
ieee: Z. A. Schaaf et al., “WDFY3 mutation alters laminar position and morphology
of cortical neurons,” Molecular Autism, vol. 13. Springer Nature, 2022.
ista: Schaaf ZA, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis
KS. 2022. WDFY3 mutation alters laminar position and morphology of cortical neurons.
Molecular Autism. 13, 27.
mla: Schaaf, Zachary A., et al. “WDFY3 Mutation Alters Laminar Position and Morphology
of Cortical Neurons.” Molecular Autism, vol. 13, 27, Springer Nature, 2022,
doi:10.1186/s13229-022-00508-3.
short: Z.A. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer,
K.S. Zarbalis, Molecular Autism 13 (2022).
date_created: 2022-06-23T14:28:55Z
date_published: 2022-06-22T00:00:00Z
date_updated: 2025-06-11T13:34:57Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1186/s13229-022-00508-3
external_id:
isi:
- '000814641400001'
pmid:
- '35733184'
file:
- access_level: open_access
checksum: 525d2618e855139089bbfc3e3d49d1b2
content_type: application/pdf
creator: dernst
date_created: 2022-06-24T08:22:59Z
date_updated: 2022-06-24T08:22:59Z
file_id: '11461'
file_name: 2022_MolecularAutism_Schaaf.pdf
file_size: 7552298
relation: main_file
success: 1
file_date_updated: 2022-06-24T08:22:59Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
keyword:
- Psychiatry and Mental health
- Developmental Biology
- Developmental Neuroscience
- Molecular Biology
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Molecular Autism
publication_identifier:
issn:
- 2040-2392
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1186/s13229-023-00539-4
scopus_import: '1'
status: public
title: WDFY3 mutation alters laminar position and morphology of cortical neurons
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: 13
year: '2022'
...
---
_id: '12282'
abstract:
- lang: eng
text: From a simple thought to a multicellular movement
acknowledgement: The authors want to thank Professors Carrie Bernecky, Tom Henzinger,
Martin Loose and Gaia Novarino for accepting to be interviewed, thus giving significant
contribution to the discussion that lead to this article.
article_number: '260017'
article_processing_charge: No
article_type: letter_note
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: Irene
full_name: Vercellino, Irene
id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
last_name: Vercellino
orcid: 0000-0001-5618-3449
citation:
ama: Amberg N, Stouffer MA, Vercellino I. Operation STEM fatale – how an equity,
diversity and inclusion initiative has brought us to reflect on the current challenges
in cell biology and science as a whole. Journal of Cell Science. 2022;135(8).
doi:10.1242/jcs.260017
apa: Amberg, N., Stouffer, M. A., & Vercellino, I. (2022). Operation STEM fatale
– how an equity, diversity and inclusion initiative has brought us to reflect
on the current challenges in cell biology and science as a whole. Journal of
Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260017
chicago: Amberg, Nicole, Melissa A Stouffer, and Irene Vercellino. “Operation STEM
Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect
on the Current Challenges in Cell Biology and Science as a Whole.” Journal
of Cell Science. The Company of Biologists, 2022. https://doi.org/10.1242/jcs.260017.
ieee: N. Amberg, M. A. Stouffer, and I. Vercellino, “Operation STEM fatale – how
an equity, diversity and inclusion initiative has brought us to reflect on the
current challenges in cell biology and science as a whole,” Journal of Cell
Science, vol. 135, no. 8. The Company of Biologists, 2022.
ista: Amberg N, Stouffer MA, Vercellino I. 2022. Operation STEM fatale – how an
equity, diversity and inclusion initiative has brought us to reflect on the current
challenges in cell biology and science as a whole. Journal of Cell Science. 135(8),
260017.
mla: Amberg, Nicole, et al. “Operation STEM Fatale – How an Equity, Diversity and
Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell
Biology and Science as a Whole.” Journal of Cell Science, vol. 135, no.
8, 260017, The Company of Biologists, 2022, doi:10.1242/jcs.260017.
short: N. Amberg, M.A. Stouffer, I. Vercellino, Journal of Cell Science 135 (2022).
corr_author: '1'
date_created: 2023-01-16T10:03:14Z
date_published: 2022-04-19T00:00:00Z
date_updated: 2024-10-09T21:03:55Z
day: '19'
department:
- _id: SiHi
- _id: LeSa
doi: 10.1242/jcs.260017
external_id:
isi:
- '000798123600015'
pmid:
- '35438168'
intvolume: ' 135'
isi: 1
issue: '8'
language:
- iso: eng
month: '04'
oa_version: None
pmid: 1
publication: Journal of Cell Science
publication_identifier:
eissn:
- 1477-9137
issn:
- 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Operation STEM fatale – how an equity, diversity and inclusion initiative has
brought us to reflect on the current challenges in cell biology and science as a
whole
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 135
year: '2022'
...
---
_id: '12283'
abstract:
- lang: eng
text: Neurons extend axons to form the complex circuitry of the mature brain. This
depends on the coordinated response and continuous remodelling of the microtubule
and F-actin networks in the axonal growth cone. Growth cone architecture remains
poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron
growth cones using cryo-electron tomography to directly visualise their three-dimensional
subcellular architecture with molecular detail. Our data showed that the hexagonal
arrays of actin bundles that form filopodia penetrate and terminate deep within
the growth cone interior. We directly observed the modulation of these and other
growth cone actin bundles by alteration of individual F-actin helical structures.
Microtubules with blunt, slightly flared or gently curved ends predominated in
the growth cone, frequently contained lumenal particles and exhibited lattice
defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental
cytoskeleton regulator, on growth cone cytoskeleton showed no major anomalies
in overall growth cone organisation or in F-actin subpopulations. However, our
data suggested that microtubules sustained more structural defects, highlighting
the importance of microtubule integrity during growth cone migration.
acknowledgement: "J.A. was supported by a grant from the Medical Research Council
(MRC), UK (MR/R000352/1) to C.A.M. Cryo-EM data were collected on equipment funded
by the Wellcome Trust, UK (079605/Z/06/Z) and the Biotechnology and Biological Sciences
Research Council (BBSRC) UK (BB/L014211/1). F.F.’s salary and institute were supported
by Inserm (Institut National de la Santé et de la Recherche Médicale), CNRS (Centre
National de la Recherche Scientifique) and Sorbonne Université. F.F.’s group was
particularly supported by Agence Nationale de la\r\nRecherche (ANR-16-CE16-0011-03)
and Seventh Framework Programme (EUHEALTH-\r\n2013, DESIRE, N° 60253; also funding
M.S.’s salary) and the European Cooperation in Science and Technology (COST Action
CA16118). Open Access funding provided by Birkbeck College: Birkbeck University
of London. Deposited in PMC for immediate release."
article_number: '259234'
article_processing_charge: No
article_type: original
author:
- first_name: Joseph
full_name: Atherton, Joseph
last_name: Atherton
- first_name: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: Fiona
full_name: Francis, Fiona
last_name: Francis
- first_name: Carolyn A.
full_name: Moores, Carolyn A.
last_name: Moores
citation:
ama: Atherton J, Stouffer MA, Francis F, Moores CA. Visualising the cytoskeletal
machinery in neuronal growth cones using cryo-electron tomography. Journal
of Cell Science. 2022;135(7). doi:10.1242/jcs.259234
apa: Atherton, J., Stouffer, M. A., Francis, F., & Moores, C. A. (2022). Visualising
the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography.
Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.259234
chicago: Atherton, Joseph, Melissa A Stouffer, Fiona Francis, and Carolyn A. Moores.
“Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron
Tomography.” Journal of Cell Science. The Company of Biologists, 2022.
https://doi.org/10.1242/jcs.259234.
ieee: J. Atherton, M. A. Stouffer, F. Francis, and C. A. Moores, “Visualising the
cytoskeletal machinery in neuronal growth cones using cryo-electron tomography,”
Journal of Cell Science, vol. 135, no. 7. The Company of Biologists, 2022.
ista: Atherton J, Stouffer MA, Francis F, Moores CA. 2022. Visualising the cytoskeletal
machinery in neuronal growth cones using cryo-electron tomography. Journal of
Cell Science. 135(7), 259234.
mla: Atherton, Joseph, et al. “Visualising the Cytoskeletal Machinery in Neuronal
Growth Cones Using Cryo-Electron Tomography.” Journal of Cell Science,
vol. 135, no. 7, 259234, The Company of Biologists, 2022, doi:10.1242/jcs.259234.
short: J. Atherton, M.A. Stouffer, F. Francis, C.A. Moores, Journal of Cell Science
135 (2022).
date_created: 2023-01-16T10:03:24Z
date_published: 2022-04-01T00:00:00Z
date_updated: 2023-08-04T10:28:34Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1242/jcs.259234
external_id:
isi:
- '000783840400010'
pmid:
- '35383828'
file:
- access_level: open_access
checksum: 4346ed32cb7c89a8ca051c7da68a9a1c
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T11:41:01Z
date_updated: 2023-01-30T11:41:01Z
file_id: '12461'
file_name: 2022_JourCellBiology_Atherton.pdf
file_size: 13868733
relation: main_file
success: 1
file_date_updated: 2023-01-30T11:41:01Z
has_accepted_license: '1'
intvolume: ' 135'
isi: 1
issue: '7'
keyword:
- Cell Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Science
publication_identifier:
eissn:
- 1477-9137
issn:
- 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron
tomography
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 135
year: '2022'
...
---
_id: '17067'
abstract:
- lang: eng
text: 'Human doublecortin (DCX) mutations are associated with severe brain malformations
leading to aberrant neuron positioning (heterotopia), intellectual disability
and epilepsy. DCX is a microtubule-associated protein which plays a key role during
neurodevelopment in neuronal migration and differentiation. Dcx knockout (KO)
mice show disorganized hippocampal pyramidal neurons. The CA2/CA3 pyramidal cell
layer is present as two abnormal layers and disorganized CA3 KO pyramidal neurons
are also more excitable than wild-type (WT) cells. To further identify abnormalities,
we characterized Dcx KO hippocampal neurons at subcellular, molecular and ultrastructural
levels. Severe defects were observed in mitochondria, affecting number and distribution.
Also, the Golgi apparatus was visibly abnormal, increased in volume and abnormally
organized. Transcriptome analyses from laser microdissected hippocampal tissue
at postnatal day 60 (P60) highlighted organelle abnormalities. Ultrastructural
studies of CA3 cells performed in P60 (young adult) and > 9 months (mature) tissue
showed that organelle defects are persistent throughout life. Locomotor activity
and fear memory of young and mature adults were also abnormal: Dcx KO mice consistently
performed less well than WT littermates, with defects becoming more severe with
age. Thus, we show that disruption of a neurodevelopmentally-regulated gene can
lead to permanent organelle anomalies contributing to abnormal adult behavior.'
acknowledgement: "We thank Sylvie Dumont for initial aid with laser microdissection
and G. Martinez-Lorenzana for experimental help with electron microscopy. We thank
the animal experimentation facility and cellular and tissue imaging platforms at
the Institut du Fer à Moulin, supported also by the Région Ile de France and the
FRC Rotary. The Francis lab was associated with the BioPsy Labex project and the
Ecole des Neurosciences de Paris Ile-de-France (ENP) network. Our salaries and lab
were supported by Inserm, the Centre national de la recherche scientifique (CNRS)
and Sorbonne University. The Francis group obtained the following funding contributing
to this project: the European Union (EU- HEALTH-2013, DESIRE, N° 60253), the JTC
2015 Neurodevelopmental Disorders affiliated with the French Agence National de
la Recherche (for \r\nNEURON8-Full- 815-006 STEM-MCD, to FF), E-Rare-3, the ERA-Net
for Research on Rare Diseases affiliated with the French ANR (ERARE18-049), the
European Cooperation on Science and Technology (COST Action CA16118)."
article_number: '105702'
article_processing_charge: Yes
article_type: original
author:
- first_name: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: R.
full_name: Khalaf-Nazzal, R.
last_name: Khalaf-Nazzal
- first_name: C.
full_name: Cifuentes-Diaz, C.
last_name: Cifuentes-Diaz
- first_name: G.
full_name: Albertini, G.
last_name: Albertini
- first_name: E.
full_name: Bandet, E.
last_name: Bandet
- first_name: G.
full_name: Grannec, G.
last_name: Grannec
- first_name: V.
full_name: Lavilla, V.
last_name: Lavilla
- first_name: J.-F.
full_name: Deleuze, J.-F.
last_name: Deleuze
- first_name: R.
full_name: Olaso, R.
last_name: Olaso
- first_name: M.
full_name: Nosten-Bertrand, M.
last_name: Nosten-Bertrand
- first_name: F.
full_name: Francis, F.
last_name: Francis
citation:
ama: Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, et al. Doublecortin mutation
leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal
pyramidal cells. Neurobiology of Disease. 2022;168. doi:10.1016/j.nbd.2022.105702
apa: Stouffer, M. A., Khalaf-Nazzal, R., Cifuentes-Diaz, C., Albertini, G., Bandet,
E., Grannec, G., … Francis, F. (2022). Doublecortin mutation leads to persistent
defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal
cells. Neurobiology of Disease. Elsevier. https://doi.org/10.1016/j.nbd.2022.105702
chicago: Stouffer, Melissa A, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini,
E. Bandet, G. Grannec, V. Lavilla, et al. “Doublecortin Mutation Leads to Persistent
Defects in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal
Cells.” Neurobiology of Disease. Elsevier, 2022. https://doi.org/10.1016/j.nbd.2022.105702.
ieee: M. A. Stouffer et al., “Doublecortin mutation leads to persistent defects
in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells,”
Neurobiology of Disease, vol. 168. Elsevier, 2022.
ista: Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, Albertini G, Bandet E, Grannec
G, Lavilla V, Deleuze J-F, Olaso R, Nosten-Bertrand M, Francis F. 2022. Doublecortin
mutation leads to persistent defects in the Golgi apparatus and mitochondria in
adult hippocampal pyramidal cells. Neurobiology of Disease. 168, 105702.
mla: Stouffer, Melissa A., et al. “Doublecortin Mutation Leads to Persistent Defects
in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal Cells.”
Neurobiology of Disease, vol. 168, 105702, Elsevier, 2022, doi:10.1016/j.nbd.2022.105702.
short: M.A. Stouffer, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini, E. Bandet,
G. Grannec, V. Lavilla, J.-F. Deleuze, R. Olaso, M. Nosten-Bertrand, F. Francis,
Neurobiology of Disease 168 (2022).
date_created: 2024-05-29T06:10:05Z
date_published: 2022-06-15T00:00:00Z
date_updated: 2024-08-06T06:57:39Z
day: '15'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.nbd.2022.105702
external_id:
pmid:
- '35339680'
file:
- access_level: open_access
checksum: b705d3d23d0b424ba29920be7ab64c23
content_type: application/pdf
creator: dernst
date_created: 2024-08-06T06:54:24Z
date_updated: 2024-08-06T06:54:24Z
file_id: '17398'
file_name: 2022_NeurobioDisease_Stouffer.pdf
file_size: 8890818
relation: main_file
success: 1
file_date_updated: 2024-08-06T06:54:24Z
has_accepted_license: '1'
intvolume: ' 168'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Neurobiology of Disease
publication_identifier:
issn:
- 0969-9961
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Doublecortin mutation leads to persistent defects in the Golgi apparatus and
mitochondria in adult hippocampal pyramidal cells
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: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 168
year: '2022'
...
---
_id: '10764'
abstract:
- lang: eng
text: Presynaptic glutamate replenishment is fundamental to brain function. In high
activity regimes, such as epileptic episodes, this process is thought to rely
on the glutamate-glutamine cycle between neurons and astrocytes. However the presence
of an astroglial glutamine supply, as well as its functional relevance in vivo
in the healthy brain remain controversial, partly due to a lack of tools that
can directly examine glutamine transfer. Here, we generated a fluorescent probe
that tracks glutamine in live cells, which provides direct visual evidence of
an activity-dependent glutamine supply from astroglial networks to presynaptic
structures under physiological conditions. This mobilization is mediated by connexin43,
an astroglial protein with both gap-junction and hemichannel functions, and is
essential for synaptic transmission and object recognition memory. Our findings
uncover an indispensable recruitment of astroglial glutamine in physiological
synaptic activity and memory via an unconventional pathway, thus providing an
astrocyte basis for cognitive processes.
acknowledgement: 'We thank D. Mazaud and. J. Cazères for technical assistance. This
work was supported by grants from the European Research Council (Consolidator grant
#683154) and European Union’s Horizon 2020 research and innovation program (Marie
Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD) to N.R.
and from FP7-PEOPLE Marie Curie Intra-European Fellowship for career development
(grant #622289) to G.C.'
article_number: '753'
article_processing_charge: No
article_type: original
author:
- 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: Danijela
full_name: Bataveljic, Danijela
last_name: Bataveljic
- first_name: Josien
full_name: Visser, Josien
last_name: Visser
- first_name: Naresh
full_name: Kumar, Naresh
last_name: Kumar
- first_name: Julien
full_name: Moulard, Julien
last_name: Moulard
- first_name: Glenn
full_name: Dallérac, Glenn
last_name: Dallérac
- first_name: Daria
full_name: Mozheiko, Daria
last_name: Mozheiko
- first_name: Astrid
full_name: Rollenhagen, Astrid
last_name: Rollenhagen
- first_name: Pascal
full_name: Ezan, Pascal
last_name: Ezan
- first_name: Cédric
full_name: Mongin, Cédric
last_name: Mongin
- first_name: Oana
full_name: Chever, Oana
last_name: Chever
- first_name: Alexis Pierre
full_name: Bemelmans, Alexis Pierre
last_name: Bemelmans
- first_name: Joachim
full_name: Lübke, Joachim
last_name: Lübke
- first_name: Isabelle
full_name: Leray, Isabelle
last_name: Leray
- first_name: Nathalie
full_name: Rouach, Nathalie
last_name: Rouach
citation:
ama: Cheung GT, Bataveljic D, Visser J, et al. Physiological synaptic activity and
recognition memory require astroglial glutamine. Nature Communications.
2022;13. doi:10.1038/s41467-022-28331-7
apa: Cheung, G. T., Bataveljic, D., Visser, J., Kumar, N., Moulard, J., Dallérac,
G., … Rouach, N. (2022). Physiological synaptic activity and recognition memory
require astroglial glutamine. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28331-7
chicago: Cheung, Giselle T, Danijela Bataveljic, Josien Visser, Naresh Kumar, Julien
Moulard, Glenn Dallérac, Daria Mozheiko, et al. “Physiological Synaptic Activity
and Recognition Memory Require Astroglial Glutamine.” Nature Communications.
Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28331-7.
ieee: G. T. Cheung et al., “Physiological synaptic activity and recognition
memory require astroglial glutamine,” Nature Communications, vol. 13. Springer
Nature, 2022.
ista: Cheung GT, Bataveljic D, Visser J, Kumar N, Moulard J, Dallérac G, Mozheiko
D, Rollenhagen A, Ezan P, Mongin C, Chever O, Bemelmans AP, Lübke J, Leray I,
Rouach N. 2022. Physiological synaptic activity and recognition memory require
astroglial glutamine. Nature Communications. 13, 753.
mla: Cheung, Giselle T., et al. “Physiological Synaptic Activity and Recognition
Memory Require Astroglial Glutamine.” Nature Communications, vol. 13, 753,
Springer Nature, 2022, doi:10.1038/s41467-022-28331-7.
short: G.T. Cheung, D. Bataveljic, J. Visser, N. Kumar, J. Moulard, G. Dallérac,
D. Mozheiko, A. Rollenhagen, P. Ezan, C. Mongin, O. Chever, A.P. Bemelmans, J.
Lübke, I. Leray, N. Rouach, Nature Communications 13 (2022).
date_created: 2022-02-20T23:01:30Z
date_published: 2022-02-08T00:00:00Z
date_updated: 2026-04-02T12:22:38Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-022-28331-7
external_id:
isi:
- '000757297200017'
pmid:
- '35136061'
file:
- access_level: open_access
checksum: 51d580aff2327dd957946208a9749e1a
content_type: application/pdf
creator: dernst
date_created: 2022-02-21T07:51:33Z
date_updated: 2022-02-21T07:51:33Z
file_id: '10777'
file_name: 2022_NatureCommunications_Cheung.pdf
file_size: 7910519
relation: main_file
success: 1
file_date_updated: 2022-02-21T07:51:33Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Physiological synaptic activity and recognition memory require astroglial glutamine
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: 13
year: '2022'
...
---
_id: '10791'
abstract:
- lang: eng
text: The mammalian neocortex is composed of diverse neuronal and glial cell classes
that broadly arrange in six distinct laminae. Cortical layers emerge during development
and defects in the developmental programs that orchestrate cortical lamination
are associated with neurodevelopmental diseases. The developmental principle of
cortical layer formation depends on concerted radial projection neuron migration,
from their birthplace to their final target position. Radial migration occurs
in defined sequential steps, regulated by a large array of signaling pathways.
However, based on genetic loss-of-function experiments, most studies have thus
far focused on the role of cell-autonomous gene function. Yet, cortical neuron
migration in situ is a complex process and migrating neurons traverse along diverse
cellular compartments and environments. The role of tissue-wide properties and
genetic state in radial neuron migration is however not clear. Here we utilized
mosaic analysis with double markers (MADM) technology to either sparsely or globally
delete gene function, followed by quantitative single-cell phenotyping. The MADM-based
gene ablation paradigms in combination with computational modeling demonstrated
that global tissue-wide effects predominate cell-autonomous gene function albeit
in a gene-specific manner. Our results thus suggest that the genetic landscape
in a tissue critically affects the overall migration phenotype of individual cortical
projection neurons. In a broader context, our findings imply that global tissue-wide
effects represent an essential component of the underlying etiology associated
with focal malformations of cortical development in particular, and neurological
diseases in general.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
- _id: Bio
acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
Academy of Sciences. This work also received support from IST Austria institutional
funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC
funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical
support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer
lab for discussion. This research was supported by the Scientific Service Units
of IST Austria through resources provided by the Imaging and Optics Facility, Lab
Support Facility and Preclinical Facility."
article_number: kvac009
article_processing_charge: No
article_type: original
author:
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
- first_name: Li Huei
full_name: Tsai, Li Huei
last_name: Tsai
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic
gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1).
doi:10.1093/oons/kvac009
apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter,
S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration. Oxford Open Neuroscience. Oxford University
Press. https://doi.org/10.1093/oons/kvac009
chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena
Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override
Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience.
Oxford University Press, 2022. https://doi.org/10.1093/oons/kvac009.
ieee: A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration,” Oxford Open Neuroscience, vol. 1,
no. 1. Oxford University Press, 2022.
ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM,
Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects
override cell-intrinsic gene function in radial neuron migration. Oxford Open
Neuroscience. 1(1), kvac009.
mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function
in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009,
Oxford University Press, 2022, doi:10.1093/oons/kvac009.
short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter,
C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford
Open Neuroscience 1 (2022).
corr_author: '1'
date_created: 2022-02-25T07:52:11Z
date_published: 2022-07-07T00:00:00Z
date_updated: 2026-04-07T13:29:13Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
- _id: BjHo
- _id: LifeSc
- _id: EM-Fac
doi: 10.1093/oons/kvac009
ec_funded: 1
external_id:
pmid:
- '38596707'
file:
- access_level: open_access
checksum: 822e76e056c07099d1fb27d1ece5941b
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T08:00:30Z
date_updated: 2023-08-16T08:00:30Z
file_id: '14061'
file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf
file_size: 4846551
relation: main_file
success: 1
file_date_updated: 2023-08-16T08:00:30Z
has_accepted_license: '1'
intvolume: ' 1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
publication: Oxford Open Neuroscience
publication_identifier:
eissn:
- 2753-149X
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
status: public
title: Tissue-wide effects override cell-intrinsic gene function in radial neuron
migration
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2022'
...
---
_id: '10792'
abstract:
- lang: eng
text: "Background\r\nProper cerebral cortical development depends on the tightly
orchestrated migration of newly born neurons from the inner ventricular and subventricular
zones to the outer cortical plate. Any disturbance in this process during prenatal
stages may lead to neuronal migration disorders (NMDs), which can vary in extent
from focal to global. Furthermore, NMDs show a substantial comorbidity with other
neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous
work demonstrated focal neuronal migration defects in mice carrying loss-of-function
alleles of the recognized autism risk gene WDFY3. However, the cellular origins
of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide
critical insight into WDFY3-dependent disease pathology .\r\nMethods\r\nHere,
in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic
analysis with double markers (MADM). MADM technology enabled us to genetically
distinctly track and phenotypically analyze mutant and wild type cells concomitantly
in vivo using immunofluorescent techniques.\r\nResults\r\nWe revealed a cell autonomous
requirement of WDFY3 for accurate laminar positioning of cortical projection neurons
and elimination of mispositioned cells during early postnatal life. In addition,
we identified significant deviations in dendritic arborization, as well as synaptic
density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant
neurons in Wdfy3-MADM reporter mice at postnatal stages. Limitations While Wdfy3
mutant mice have provided valuable insight into prenatal aspects of ASD pathology
that remain inaccessible to investigation in humans, like most animal models,
they do not a perfectly replicate all aspects of human ASD biology. The lack of
human data makes it indeterminate whether morphological deviations described here
apply to ASD patients.\r\nConclusions\r\n\uFEFFOur genetic approach revealed several
cell autonomous requirements of Wdfy3 in neuronal development that could underly
the pathogenic mechanisms of WDFY3-related ASD conditions. The results are also
consistent with findings in other ASD animal models and patients and suggest an
important role for Wdfy3 in regulating neuronal function and interconnectivity
in postnatal life."
article_processing_charge: No
author:
- first_name: Zachary
full_name: Schaaf, Zachary
last_name: Schaaf
- first_name: Lyvin
full_name: Tat, Lyvin
last_name: Tat
- first_name: Noemi
full_name: Cannizzaro, Noemi
last_name: Cannizzaro
- first_name: Ralph
full_name: Green, Ralph
last_name: Green
- 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
- first_name: K
full_name: Zarbalis, K
last_name: Zarbalis
citation:
ama: Schaaf Z, Tat L, Cannizzaro N, et al. WDFY3 cell autonomously controls neuronal
migration. doi:10.21203/rs.3.rs-1316167/v1
apa: Schaaf, Z., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S.,
& Zarbalis, K. (n.d.). WDFY3 cell autonomously controls neuronal migration.
Research Square. https://doi.org/10.21203/rs.3.rs-1316167/v1
chicago: Schaaf, Zachary, Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke,
Simon Hippenmeyer, and K Zarbalis. “WDFY3 Cell Autonomously Controls Neuronal
Migration.” Research Square, n.d. https://doi.org/10.21203/rs.3.rs-1316167/v1.
ieee: Z. Schaaf et al., “WDFY3 cell autonomously controls neuronal migration.”
Research Square.
ista: Schaaf Z, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis
K. WDFY3 cell autonomously controls neuronal migration. 10.21203/rs.3.rs-1316167/v1.
mla: Schaaf, Zachary, et al. WDFY3 Cell Autonomously Controls Neuronal Migration.
Research Square, doi:10.21203/rs.3.rs-1316167/v1.
short: Z. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K.
Zarbalis, (n.d.).
date_created: 2022-02-25T07:53:26Z
date_published: 2022-02-16T00:00:00Z
date_updated: 2023-10-17T13:06:52Z
day: '16'
department:
- _id: SiHi
doi: 10.21203/rs.3.rs-1316167/v1
external_id:
pmid:
- PPR454733
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.21203/rs.3.rs-1316167/v1
month: '02'
oa: 1
oa_version: Preprint
page: '30'
pmid: 1
publication_identifier:
eissn:
- 2693-5015
publication_status: submitted
publisher: Research Square
status: public
title: WDFY3 cell autonomously controls neuronal migration
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '9794'
abstract:
- lang: eng
text: 'Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular
cells that form dedicated niches for immune cell interaction and capsular fibroblasts
that build a shell around the organ. Immunological challenge causes LNs to increase
more than tenfold in size within a few days. Here, we characterized the biomechanics
of LN swelling on the cellular and organ scale. We identified lymphocyte trapping
by influx and proliferation as drivers of an outward pressure force, causing fibroblastic
reticular cells of the T-zone (TRCs) and their associated conduits to stretch.
After an initial phase of relaxation, TRCs sensed the resulting strain through
cell matrix adhesions, which coordinated local growth and remodeling of the stromal
network. While the expanded TRC network readopted its typical configuration, a
massive fibrotic reaction of the organ capsule set in and countered further organ
expansion. Thus, different fibroblast populations mechanically control LN swelling
in a multitier fashion.'
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: PreCl
- _id: LifeSc
acknowledgement: This research was supported by the Scientific Service Units of IST
Austria through resources provided by the Imaging and Optics, Electron Microscopy,
Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd
antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing
a custom 3D channel alignment script. This work was supported by a European Research
Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR
20-24603Y and Charles University PRIMUS/20/MED/013.
article_processing_charge: No
article_type: original
author:
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Tommaso
full_name: Costanzo, Tommaso
id: D93824F4-D9BA-11E9-BB12-F207E6697425
last_name: Costanzo
orcid: 0000-0001-9732-3815
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Burkhard
full_name: Ludewig, Burkhard
last_name: Ludewig
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- 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
- first_name: Wolfgang
full_name: Weninger, Wolfgang
last_name: Weninger
- 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: Sanjiv A.
full_name: Luther, Sanjiv A.
last_name: Luther
- first_name: Jens V.
full_name: Stein, Jens V.
last_name: Stein
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4
apa: Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W.,
… Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling
lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4
chicago: Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour,
Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal
Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature,
2022. https://doi.org/10.1038/s41590-022-01257-4.
ieee: F. P. Assen et al., “Multitier mechanics control stromal adaptations
in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature,
pp. 1246–1255, 2022.
ista: Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T,
Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo
EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 23, 1246–1255.
mla: Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in
Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022,
pp. 1246–55, doi:10.1038/s41590-022-01257-4.
short: F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T.
Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg,
W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology
23 (2022) 1246–1255.
corr_author: '1'
date_created: 2021-08-06T09:09:11Z
date_published: 2022-07-11T00:00:00Z
date_updated: 2025-06-11T13:52:43Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
- _id: CaHe
- _id: EdHa
- _id: EM-Fac
- _id: Bio
- _id: MiSi
doi: 10.1038/s41590-022-01257-4
ec_funded: 1
external_id:
isi:
- '000822975900002'
pmid:
- '35817845'
file:
- access_level: open_access
checksum: 628e7b49809f22c75b428842efe70c68
content_type: application/pdf
creator: dernst
date_created: 2022-07-25T07:11:32Z
date_updated: 2022-07-25T07:11:32Z
file_id: '11642'
file_name: 2022_NatureImmunology_Assen.pdf
file_size: 11475325
relation: main_file
success: 1
file_date_updated: 2022-07-25T07:11:32Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1246-1255
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: Nature Immunology
publication_identifier:
eissn:
- 1529-2916
issn:
- 1529-2908
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Multitier mechanics control stromal adaptations in swelling lymph nodes
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: 23
year: '2022'
...
---
_id: '10321'
abstract:
- lang: eng
text: Mosaic analysis with double markers (MADM) technology enables the generation
of genetic mosaic tissue in mice. MADM enables concomitant fluorescent cell labeling
and introduction of a mutation of a gene of interest with single-cell resolution.
This protocol highlights major steps for the generation of genetic mosaic tissue
and the isolation and processing of respective tissues for downstream histological
analysis. For complete details on the use and execution of this protocol, please
refer to Contreras et al. (2021).
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: This research was supported by the Scientific Service Units (SSU)
at IST Austria through resources provided by the Bioimaging (BIF) and Preclinical
Facilities (PCF). We particularly thank Mohammad Goudarzi for assistance with photography
of mouse perfusion and dissection. N.A. received support from FWF Firnberg-Programm
(T 1031). This work was also supported by IST Austria institutional funds; FWF SFB
F78 to S.H.; and the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro)
to S.H.
article_number: '100939'
article_processing_charge: Yes
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Hippenmeyer S. Genetic mosaic dissection of candidate genes in mice
using mosaic analysis with double markers. STAR Protocols. 2021;2(4). doi:10.1016/j.xpro.2021.100939
apa: Amberg, N., & Hippenmeyer, S. (2021). Genetic mosaic dissection of candidate
genes in mice using mosaic analysis with double markers. STAR Protocols.
Cell Press. https://doi.org/10.1016/j.xpro.2021.100939
chicago: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols.
Cell Press, 2021. https://doi.org/10.1016/j.xpro.2021.100939.
ieee: N. Amberg and S. Hippenmeyer, “Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers,” STAR Protocols, vol.
2, no. 4. Cell Press, 2021.
ista: Amberg N, Hippenmeyer S. 2021. Genetic mosaic dissection of candidate genes
in mice using mosaic analysis with double markers. STAR Protocols. 2(4), 100939.
mla: Amberg, Nicole, and Simon Hippenmeyer. “Genetic Mosaic Dissection of Candidate
Genes in Mice Using Mosaic Analysis with Double Markers.” STAR Protocols,
vol. 2, no. 4, 100939, Cell Press, 2021, doi:10.1016/j.xpro.2021.100939.
short: N. Amberg, S. Hippenmeyer, STAR Protocols 2 (2021).
corr_author: '1'
date_created: 2021-11-21T23:01:28Z
date_published: 2021-11-10T00:00:00Z
date_updated: 2025-04-15T08:23:07Z
day: '10'
ddc:
- '573'
department:
- _id: SiHi
doi: 10.1016/j.xpro.2021.100939
ec_funded: 1
file:
- access_level: open_access
checksum: 9e3f6d06bf583e7a8b6a9e9a60500a28
content_type: application/pdf
creator: cchlebak
date_created: 2021-11-22T08:23:58Z
date_updated: 2021-11-22T08:23:58Z
file_id: '10329'
file_name: 2021_STARProtocols_Amberg.pdf
file_size: 7309464
relation: main_file
success: 1
file_date_updated: 2021-11-22T08:23:58Z
has_accepted_license: '1'
intvolume: ' 2'
issue: '4'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
- _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: STAR Protocols
publication_identifier:
eissn:
- 2666-1667
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genetic mosaic dissection of candidate genes in mice using mosaic analysis
with double markers
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2
year: '2021'
...
---
_id: '10655'
abstract:
- lang: eng
text: "Adeno-associated viruses (AAVs) are widely used to deliver genetic material
in vivo to distinct cell types such as neurons or glial cells, allowing for targeted
manipulation. Transduction of microglia is mostly excluded from this strategy,
likely due to the cells’ heterogeneous state upon environmental changes, which
makes AAV design challenging. Here, we established the retina as a model system
for microglial AAV validation and optimization. First, we show that AAV2/6 transduced
microglia in both synaptic layers, where layer preference corresponds to the intravitreal
or subretinal delivery method. Surprisingly, we observed significantly enhanced
microglial transduction during photoreceptor degeneration. Thus, we modified the
AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E,
R576Q, K493S, and K459S), resulting in increased microglial transduction in the
outer plexiform layer. Finally, to improve microglial-specific transduction, we
validated a Cre-dependent transgene delivery cassette for use in combination with
the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future
studies optimizing AAV-mediated microglia transduction and highlight that environmental
conditions influence microglial transduction efficiency.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 715571). The research was supported by the Scientific Service
Units (SSU) of IST Austria through resources provided by the Bioimaging Facility,
the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger
and Michael Schunn for their animal colony management and support. We would also
like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally,
we would like to thank the Siegert team members for discussion about the manuscript.
article_processing_charge: Yes
article_type: original
author:
- 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: Gabriele M.
full_name: Wögenstein, Gabriele M.
last_name: Wögenstein
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
2021;23:210-224. doi:10.1016/j.omtm.2021.09.006
apa: Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert,
S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency
in the photoreceptor degenerative environment. Molecular Therapy - Methods
and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006
chicago: Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado
Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006.
ieee: M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert,
“Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical
Development, vol. 23. Elsevier, pp. 210–224, 2021.
ista: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
23, 210–224.
mla: Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24,
doi:10.1016/j.omtm.2021.09.006.
short: M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular
Therapy - Methods and Clinical Development 23 (2021) 210–224.
corr_author: '1'
date_created: 2022-01-23T23:01:28Z
date_published: 2021-12-10T00:00:00Z
date_updated: 2025-04-14T07:41:46Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
- _id: SiHi
doi: 10.1016/j.omtm.2021.09.006
ec_funded: 1
external_id:
isi:
- '000748748500019'
file:
- access_level: open_access
checksum: 77dc540e8011c5475031bdf6ccef20a6
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-24T07:43:09Z
date_updated: 2022-01-24T07:43:09Z
file_id: '10657'
file_name: 2021_MolTherMethodsClinDev_Maes.pdf
file_size: 4794147
relation: main_file
success: 1
file_date_updated: 2022-01-24T07:43:09Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 210-224
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Molecular Therapy - Methods and Clinical Development
publication_identifier:
eissn:
- 2329-0501
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2021'
...
---
_id: '8544'
abstract:
- lang: eng
text: The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic
branches, yet this hypothesis has not been causally tested in vivo in the mammalian
brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2
mediate synaptogenesis between granule cells and Purkinje cells in the molecular
layer of the cerebellar cortex. Here we show that sparse but not global knockout
of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular
layer and overelaboration in the superficial molecular layer. Developmental, overexpression,
structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis
defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner.
A generative model of dendritic growth based on competitive synaptogenesis largely
recapitulates GluD2 sparse and global knockout phenotypes. Our results support
the synaptotrophic hypothesis at initial stages of dendrite development, suggest
a second mode in which cumulative synapse formation inhibits further dendrite
growth, and highlight the importance of competition in dendrite morphogenesis.
acknowledgement: We thank M. Mishina for GluD2fl frozen embryos, T.C. Südhof and J.I.
Morgan for Cbln1fl mice, L. Anderson for help in generating the MADM alleles, W.
Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members
of the Luo lab, including J.M. Kebschull, H. Li, J. Li, T. Li, C.M. McLaughlin,
D. Pederick, J. Ren, D.C. Wang and C. Xu for discussions and critiques of the manuscript,
and M. Yuzaki for supporting Y.H.T. during the final phase of this project. Y.H.T.
was supported by a JSPS fellowship; S.A.S. was supported by a Stanford Graduate
Fellowship and an NSF Predoctoral Fellowship; L.J. is supported by a Stanford Graduate
Fellowship and an NSF Predoctoral Fellowship; M.J.W. is supported by a Burroughs
Wellcome Fund CASI Award. This work was supported by an NIH grant (R01-NS050538)
to L.L.; the European Research Council (ERC) under the European Union's Horizon
2020 research and innovations programme (No. 725780 LinPro) to S.H.; and Simons
and James S. McDonnell Foundations and an NSF CAREER award to S.G.; L.L. is an HHMI
investigator.
article_processing_charge: No
article_type: original
author:
- first_name: Yukari H.
full_name: Takeo, Yukari H.
last_name: Takeo
- first_name: S. Andrew
full_name: Shuster, S. Andrew
last_name: Shuster
- first_name: Linnie
full_name: Jiang, Linnie
last_name: Jiang
- first_name: Miley
full_name: Hu, Miley
last_name: Hu
- first_name: David J.
full_name: Luginbuhl, David J.
last_name: Luginbuhl
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Mark J.
full_name: Wagner, Mark J.
last_name: Wagner
- first_name: Surya
full_name: Ganguli, Surya
last_name: Ganguli
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
citation:
ama: Takeo YH, Shuster SA, Jiang L, et al. GluD2- and Cbln1-mediated competitive
synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron.
2021;109(4):P629-644.E8. doi:10.1016/j.neuron.2020.11.028
apa: Takeo, Y. H., Shuster, S. A., Jiang, L., Hu, M., Luginbuhl, D. J., Rülicke,
T., … Luo, L. (2021). GluD2- and Cbln1-mediated competitive synaptogenesis shapes
the dendritic arbors of cerebellar Purkinje cells. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.11.028
chicago: Takeo, Yukari H., S. Andrew Shuster, Linnie Jiang, Miley Hu, David J. Luginbuhl,
Thomas Rülicke, Ximena Contreras, et al. “GluD2- and Cbln1-Mediated Competitive
Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron.
Elsevier, 2021. https://doi.org/10.1016/j.neuron.2020.11.028.
ieee: Y. H. Takeo et al., “GluD2- and Cbln1-mediated competitive synaptogenesis
shapes the dendritic arbors of cerebellar Purkinje cells,” Neuron, vol.
109, no. 4. Elsevier, p. P629–644.E8, 2021.
ista: Takeo YH, Shuster SA, Jiang L, Hu M, Luginbuhl DJ, Rülicke T, Contreras X,
Hippenmeyer S, Wagner MJ, Ganguli S, Luo L. 2021. GluD2- and Cbln1-mediated competitive
synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron.
109(4), P629–644.E8.
mla: Takeo, Yukari H., et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis
Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron, vol.
109, no. 4, Elsevier, 2021, p. P629–644.E8, doi:10.1016/j.neuron.2020.11.028.
short: Y.H. Takeo, S.A. Shuster, L. Jiang, M. Hu, D.J. Luginbuhl, T. Rülicke, X.
Contreras, S. Hippenmeyer, M.J. Wagner, S. Ganguli, L. Luo, Neuron 109 (2021)
P629–644.E8.
date_created: 2020-09-21T11:59:47Z
date_published: 2021-02-17T00:00:00Z
date_updated: 2025-09-10T09:58:28Z
day: '17'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2020.11.028
ec_funded: 1
external_id:
isi:
- '000632657400006'
pmid:
- '33352118'
intvolume: ' 109'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.06.14.151258
month: '02'
oa: 1
oa_version: Preprint
page: P629-644.E8
pmid: 1
project:
- _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: Neuron
publication_identifier:
eissn:
- 1097-4199
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors
of cerebellar Purkinje cells
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 109
year: '2021'
...
---
_id: '8546'
abstract:
- lang: eng
text: Brain neurons arise from relatively few progenitors generating an enormous
diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain
neurogenesis is thought to be that excitatory and inhibitory neurons derive from
separate, spatially segregated progenitors. Whether bi-potential progenitors with
an intrinsic capacity to generate both lineages exist and how such a fate decision
may be regulated are unknown. Using cerebellar development as a model, we discover
that individual progenitors can give rise to both inhibitory and excitatory lineages.
Gradations of Notch activity determine the fates of the progenitors and their
daughters. Daughters with the highest levels of Notch activity retain the progenitor
fate, while intermediate levels of Notch activity generate inhibitory neurons,
and daughters with very low levels of Notch signaling adopt the excitatory fate.
Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating
the ratio of excitatory to inhibitory neurons from common progenitors.
acknowledgement: This work was supported by the program “Investissements d’avenir”
ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished
Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard
Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under
the European Union’s Horizon 2020 research and innovation programme grant agreement
no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships
from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the
Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice
facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06
and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.”
Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant,
and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility,
iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical
support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP
transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe
Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2
mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies.
B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .
article_number: '109208'
article_processing_charge: No
article_type: original
author:
- first_name: Tingting
full_name: Zhang, Tingting
last_name: Zhang
- first_name: Tengyuan
full_name: Liu, Tengyuan
last_name: Liu
- first_name: Natalia
full_name: Mora, Natalia
last_name: Mora
- first_name: Justine
full_name: Guegan, Justine
last_name: Guegan
- first_name: Mathilde
full_name: Bertrand, Mathilde
last_name: Bertrand
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Marica
full_name: Anderle, Marica
last_name: Anderle
- first_name: Natasha
full_name: Danda, Natasha
last_name: Danda
- first_name: Luca
full_name: Tiberi, Luca
last_name: Tiberi
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Bassem A.
full_name: Hassan, Bassem A.
last_name: Hassan
citation:
ama: Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons
from common progenitors via Notch signaling in the cerebellum. Cell Reports.
2021;35(10). doi:10.1016/j.celrep.2021.109208
apa: Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan,
B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors
via Notch signaling in the cerebellum. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109208
chicago: Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand,
Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory
Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell
Reports. Elsevier, 2021. https://doi.org/10.1016/j.celrep.2021.109208.
ieee: T. Zhang et al., “Generation of excitatory and inhibitory neurons from
common progenitors via Notch signaling in the cerebellum,” Cell Reports,
vol. 35, no. 10. Elsevier, 2021.
ista: Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher
C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of
excitatory and inhibitory neurons from common progenitors via Notch signaling
in the cerebellum. Cell Reports. 35(10), 109208.
mla: Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from
Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports,
vol. 35, no. 10, 109208, Elsevier, 2021, doi:10.1016/j.celrep.2021.109208.
short: T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen,
C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell
Reports 35 (2021).
date_created: 2020-09-21T12:00:48Z
date_published: 2021-06-08T00:00:00Z
date_updated: 2026-04-02T11:52:30Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.celrep.2021.109208
ec_funded: 1
external_id:
isi:
- '000659894300001'
pmid:
- '34107249 '
file:
- access_level: open_access
checksum: 7def3d42ebc8f5675efb6f38819e3e2e
content_type: application/pdf
creator: cziletti
date_created: 2021-06-15T14:01:35Z
date_updated: 2021-06-15T14:01:35Z
file_id: '9554'
file_name: 2021_CellReports_Zhang.pdf
file_size: 8900385
relation: main_file
success: 1
file_date_updated: 2021-06-15T14:01:35Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '10'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
publication: Cell Reports
publication_identifier:
eissn:
- ' 2211-1247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- relation: earlier_version
url: https://doi.org/10.1101/2020.03.18.997205
scopus_import: '1'
status: public
title: Generation of excitatory and inhibitory neurons from common progenitors via
Notch signaling in the cerebellum
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: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 35
year: '2021'
...
---
_id: '9073'
abstract:
- lang: eng
text: The sensory and cognitive abilities of the mammalian neocortex are underpinned
by intricate columnar and laminar circuits formed from an array of diverse neuronal
populations. One approach to determining how interactions between these circuit
components give rise to complex behavior is to investigate the rules by which
cortical circuits are formed and acquire functionality during development. This
review summarizes recent research on the development of the neocortex, from genetic
determination in neural stem cells through to the dynamic role that specific neuronal
populations play in the earliest circuits of neocortex, and how they contribute
to emergent function and cognition. While many of these endeavors take advantage
of model systems, consideration will also be given to advances in our understanding
of activity in nascent human circuits. Such cross-species perspective is imperative
when investigating the mechanisms underlying the dysfunction of early neocortical
circuits in neurodevelopmental disorders, so that one can identify targets amenable
to therapeutic intervention.
acknowledgement: Work in the I.L.H.-O. laboratory was supported by European Research
Council Grant ERC-2015-CoG 681577 and German Research Foundation Ha 4466/10-1, Ha4466/11-1,
Ha4466/12-1, SPP 1665, and SFB 936B5. Work in the S.J.B.B. laboratory was supported
by Biotechnology and Biological Sciences Research Council BB/P003796/1, Medical
Research Council MR/K004387/1 and MR/T033320/1, Wellcome Trust 215199/Z/19/Z and
102386/Z/13/Z, and John Fell Fund. Work in the S.H. laboratory was supported by
European Research Council Grants ERC-2016-CoG 725780 LinPro and FWF SFB F78. This
work was supported by National Institutes of Health Grant NIMH 1R01MH110553 to N.V.D.M.G.
Work in the J.A.C. laboratory was supported by the Ludwig Family Foundation, Simons
Foundation SFARI Research Award, and National Institutes of Health/National Institute
of Mental Health R01 MH102365 and R01MH113852. The B.V. laboratory was supported
by Whitehall Foundation 2017-12-73, National Science Foundation 1736028, National
Institutes of Health, National Institute of General Medical Sciences R01GM134363-01,
and Halıcıoğlu Data Science Institute Fellowship. This work was supported by the
University of California San Diego School of Medicine.
article_processing_charge: No
article_type: original
author:
- first_name: Ileana L.
full_name: Hanganu-Opatz, Ileana L.
last_name: Hanganu-Opatz
- first_name: Simon J. B.
full_name: Butt, Simon J. B.
last_name: Butt
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Natalia V.
full_name: De Marco García, Natalia V.
last_name: De Marco García
- first_name: Jessica A.
full_name: Cardin, Jessica A.
last_name: Cardin
- first_name: Bradley
full_name: Voytek, Bradley
last_name: Voytek
- first_name: Alysson R.
full_name: Muotri, Alysson R.
last_name: Muotri
citation:
ama: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, et al. The logic of developing neocortical
circuits in health and disease. The Journal of Neuroscience. 2021;41(5):813-822.
doi:10.1523/jneurosci.1655-20.2020
apa: Hanganu-Opatz, I. L., Butt, S. J. B., Hippenmeyer, S., De Marco García, N.
V., Cardin, J. A., Voytek, B., & Muotri, A. R. (2021). The logic of developing
neocortical circuits in health and disease. The Journal of Neuroscience.
Society for Neuroscience. https://doi.org/10.1523/jneurosci.1655-20.2020
chicago: Hanganu-Opatz, Ileana L., Simon J. B. Butt, Simon Hippenmeyer, Natalia
V. De Marco García, Jessica A. Cardin, Bradley Voytek, and Alysson R. Muotri.
“The Logic of Developing Neocortical Circuits in Health and Disease.” The Journal
of Neuroscience. Society for Neuroscience, 2021. https://doi.org/10.1523/jneurosci.1655-20.2020.
ieee: I. L. Hanganu-Opatz et al., “The logic of developing neocortical circuits
in health and disease,” The Journal of Neuroscience, vol. 41, no. 5. Society
for Neuroscience, pp. 813–822, 2021.
ista: Hanganu-Opatz IL, Butt SJB, Hippenmeyer S, De Marco García NV, Cardin JA,
Voytek B, Muotri AR. 2021. The logic of developing neocortical circuits in health
and disease. The Journal of Neuroscience. 41(5), 813–822.
mla: Hanganu-Opatz, Ileana L., et al. “The Logic of Developing Neocortical Circuits
in Health and Disease.” The Journal of Neuroscience, vol. 41, no. 5, Society
for Neuroscience, 2021, pp. 813–22, doi:10.1523/jneurosci.1655-20.2020.
short: I.L. Hanganu-Opatz, S.J.B. Butt, S. Hippenmeyer, N.V. De Marco García, J.A.
Cardin, B. Voytek, A.R. Muotri, The Journal of Neuroscience 41 (2021) 813–822.
date_created: 2021-02-03T12:23:51Z
date_published: 2021-02-03T00:00:00Z
date_updated: 2025-04-15T08:23:06Z
day: '03'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1523/jneurosci.1655-20.2020
ec_funded: 1
external_id:
isi:
- '000616763400002'
pmid:
- '33431633'
file:
- access_level: open_access
checksum: 578fd7ed1a0aef74bce61bea2d987b33
content_type: application/pdf
creator: dernst
date_created: 2022-05-27T06:59:55Z
date_updated: 2022-05-27T06:59:55Z
file_id: '11414'
file_name: 2021_JourNeuroscience_Hanganu.pdf
file_size: 1031150
relation: main_file
success: 1
file_date_updated: 2022-05-27T06:59:55Z
has_accepted_license: '1'
intvolume: ' 41'
isi: 1
issue: '5'
keyword:
- General Neuroscience
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 813-822
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _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: The Journal of Neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: The logic of developing neocortical circuits in health and disease
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 41
year: '2021'
...
---
_id: '9188'
abstract:
- lang: eng
text: Genomic imprinting is an epigenetic mechanism that results in parental allele-specific
expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental
regulators and play pivotal roles in many biological processes such as nutrient
transfer from the mother to offspring and neuronal development. Imprinted genes
are also involved in human disease, including neurodevelopmental disorders, and
often occur in clusters that are regulated by a common imprint control region
(ICR). In extra-embryonic tissues ICRs can act over large distances, with the
largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical
imprinted expression that shows near exclusive maternal or paternal expression,
widespread biased imprinted expression has been identified mainly in brain. In
this review we discuss recent developments mapping cell type specific imprinted
expression in extra-embryonic tissues and neocortex in the mouse. We highlight
the advantages of using an inducible uniparental chromosome disomy (UPD) system
to generate cells carrying either two maternal or two paternal copies of a specific
chromosome to analyze the functional consequences of genomic imprinting. Mosaic
Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant
induction of UPD sparsely in specific cell types, and thus to over-express or
suppress all imprinted genes on that chromosome. To illustrate the utility of
this technique, we explain how MADM-induced UPD revealed new insights about the
function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs
led to identification of highly cell type specific phenotypes related to perturbed
imprinted expression in the mouse neocortex. Finally, we give an outlook on how
MADM could be used to probe cell type specific imprinted expression in other tissues
in mouse, particularly in extra-embryonic tissues.
acknowledgement: We thank Melissa Stouffer for critically reading the manuscript.
This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung
n[f + b] life science call grant (C13-002) to S.H. and the European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation program (grant
agreement 725780 LinPro) to S.H.
article_number: '104986'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Quanah
full_name: Hudson, Quanah
last_name: Hudson
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. Inducible uniparental chromosome
disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry
International. 2021;145(5). doi:10.1016/j.neuint.2021.104986
apa: Pauler, F., Hudson, Q., Laukoter, S., & Hippenmeyer, S. (2021). Inducible
uniparental chromosome disomy to probe genomic imprinting at single-cell level
in brain and beyond. Neurochemistry International. Elsevier. https://doi.org/10.1016/j.neuint.2021.104986
chicago: Pauler, Florian, Quanah Hudson, Susanne Laukoter, and Simon Hippenmeyer.
“Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell
Level in Brain and Beyond.” Neurochemistry International. Elsevier, 2021.
https://doi.org/10.1016/j.neuint.2021.104986.
ieee: F. Pauler, Q. Hudson, S. Laukoter, and S. Hippenmeyer, “Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond,” Neurochemistry International, vol. 145, no. 5. Elsevier, 2021.
ista: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. 2021. Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond. Neurochemistry International. 145(5), 104986.
mla: Pauler, Florian, et al. “Inducible Uniparental Chromosome Disomy to Probe Genomic
Imprinting at Single-Cell Level in Brain and Beyond.” Neurochemistry International,
vol. 145, no. 5, 104986, Elsevier, 2021, doi:10.1016/j.neuint.2021.104986.
short: F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International
145 (2021).
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title: Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell
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