---
_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  Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members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. <i>Neuron</i>.
    2021;109(4):P629-644.E8. doi:<a href="https://doi.org/10.1016/j.neuron.2020.11.028">10.1016/j.neuron.2020.11.028</a>
  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. <i>Neuron</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.neuron.2020.11.028">https://doi.org/10.1016/j.neuron.2020.11.028</a>
  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.” <i>Neuron</i>.
    Elsevier, 2021. <a href="https://doi.org/10.1016/j.neuron.2020.11.028">https://doi.org/10.1016/j.neuron.2020.11.028</a>.
  ieee: Y. H. Takeo <i>et al.</i>, “GluD2- and Cbln1-mediated competitive synaptogenesis
    shapes the dendritic arbors of cerebellar Purkinje cells,” <i>Neuron</i>, 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.” <i>Neuron</i>, vol.
    109, no. 4, Elsevier, 2021, p. P629–644.E8, doi:<a href="https://doi.org/10.1016/j.neuron.2020.11.028">10.1016/j.neuron.2020.11.028</a>.
  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: 2024-03-06T12:12:48Z
day: '17'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2020.11.028
ec_funded: 1
intvolume: '       109'
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
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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. <i>Cell Reports</i>.
    2021;35(10). doi:<a href="https://doi.org/10.1016/j.celrep.2021.109208">10.1016/j.celrep.2021.109208</a>
  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. <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2021.109208">https://doi.org/10.1016/j.celrep.2021.109208</a>
  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.” <i>Cell
    Reports</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.celrep.2021.109208">https://doi.org/10.1016/j.celrep.2021.109208</a>.
  ieee: T. Zhang <i>et al.</i>, “Generation of excitatory and inhibitory neurons from
    common progenitors via Notch signaling in the cerebellum,” <i>Cell Reports</i>,
    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.” <i>Cell Reports</i>,
    vol. 35, no. 10, 109208, Elsevier, 2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109208">10.1016/j.celrep.2021.109208</a>.
  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: 2023-08-04T11:00:48Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.celrep.2021.109208
ec_funded: 1
external_id:
  isi:
  - '000659894300001'
  pmid:
  - '34107249 '
file:
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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:
  - ' 22111247'
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '9603'
abstract:
- lang: eng
  text: Mosaic analysis with double markers (MADM) offers one approach to visualize
    and concomitantly manipulate genetically defined cells in mice with single-cell
    resolution. MADM applications include the analysis of lineage, single-cell morphology
    and physiology, genomic imprinting phenotypes, and dissection of cell-autonomous
    gene functions in vivo in health and disease. Yet, MADM can only be applied to
    <25% of all mouse genes on select chromosomes to date. To overcome this limitation,
    we generate transgenic mice with knocked-in MADM cassettes near the centromeres
    of all 19 autosomes and validate their use across organs. With this resource,
    >96% of the entire mouse genome can now be subjected to single-cell genetic mosaic
    analysis. Beyond a proof of principle, we apply our MADM library to systematically
    trace sister chromatid segregation in distinct mitotic cell lineages. We find
    striking chromosome-specific biases in segregation patterns, reflecting a putative
    mechanism for the asymmetric segregation of genetic determinants in somatic stem
    cell division.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank the Bioimaging, Life Science, and Pre-Clinical Facilities
  at IST Austria; M.P. Postiglione, C. Simbriger, K. Valoskova, C. Schwayer, T. Hussain,
  M. Pieber, and V. Wimmer for initial experiments, technical support, and/or assistance;
  R. Shigemoto for sharing iv (Dnah11 mutant) mice; and M. Sixt and all members of
  the Hippenmeyer lab for discussion. This work was supported by National Institutes
  of Health grants ( R01-NS050580 to L.L. and F32MH096361 to L.A.S.). L.L. is an investigator
  of HHMI. N.A. received support from FWF Firnberg-Programm ( T 1031 ). A.H.H. is
  a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences . This
  work also received support from IST Austria institutional funds , FWF SFB F78 to
  S.H., 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.,
  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: '109274'
article_processing_charge: No
article_type: original
author:
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- first_name: Amarbayasgalan
  full_name: Davaatseren, Amarbayasgalan
  id: 70ADC922-B424-11E9-99E3-BA18E6697425
  last_name: Davaatseren
- first_name: Andi H
  full_name: Hansen, Andi H
  id: 38853E16-F248-11E8-B48F-1D18A9856A87
  last_name: Hansen
- first_name: Johanna
  full_name: Sonntag, Johanna
  id: 32FE7D7C-F248-11E8-B48F-1D18A9856A87
  last_name: Sonntag
- first_name: Lill
  full_name: Andersen, Lill
  last_name: Andersen
- first_name: Tina
  full_name: Bernthaler, Tina
  last_name: Bernthaler
- 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: Randy L.
  full_name: Johnson, Randy L.
  last_name: Johnson
- first_name: Lindsay A.
  full_name: Schwarz, Lindsay A.
  last_name: Schwarz
- first_name: Liqun
  full_name: Luo, Liqun
  last_name: Luo
- 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: Contreras X, Amberg N, Davaatseren A, et al. A genome-wide library of MADM
    mice for single-cell genetic mosaic analysis. <i>Cell Reports</i>. 2021;35(12).
    doi:<a href="https://doi.org/10.1016/j.celrep.2021.109274">10.1016/j.celrep.2021.109274</a>
  apa: Contreras, X., Amberg, N., Davaatseren, A., Hansen, A. H., Sonntag, J., Andersen,
    L., … Hippenmeyer, S. (2021). A genome-wide library of MADM mice for single-cell
    genetic mosaic analysis. <i>Cell Reports</i>. Cell Press. <a href="https://doi.org/10.1016/j.celrep.2021.109274">https://doi.org/10.1016/j.celrep.2021.109274</a>
  chicago: Contreras, Ximena, Nicole Amberg, Amarbayasgalan Davaatseren, Andi H Hansen,
    Johanna Sonntag, Lill Andersen, Tina Bernthaler, et al. “A Genome-Wide Library
    of MADM Mice for Single-Cell Genetic Mosaic Analysis.” <i>Cell Reports</i>. Cell
    Press, 2021. <a href="https://doi.org/10.1016/j.celrep.2021.109274">https://doi.org/10.1016/j.celrep.2021.109274</a>.
  ieee: X. Contreras <i>et al.</i>, “A genome-wide library of MADM mice for single-cell
    genetic mosaic analysis,” <i>Cell Reports</i>, vol. 35, no. 12. Cell Press, 2021.
  ista: Contreras X, Amberg N, Davaatseren A, Hansen AH, Sonntag J, Andersen L, Bernthaler
    T, Streicher C, Heger A-M, Johnson RL, Schwarz LA, Luo L, Rülicke T, Hippenmeyer
    S. 2021. A genome-wide library of MADM mice for single-cell genetic mosaic analysis.
    Cell Reports. 35(12), 109274.
  mla: Contreras, Ximena, et al. “A Genome-Wide Library of MADM Mice for Single-Cell
    Genetic Mosaic Analysis.” <i>Cell Reports</i>, vol. 35, no. 12, 109274, Cell Press,
    2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109274">10.1016/j.celrep.2021.109274</a>.
  short: X. Contreras, N. Amberg, A. Davaatseren, A.H. Hansen, J. Sonntag, L. Andersen,
    T. Bernthaler, C. Streicher, A.-M. Heger, R.L. Johnson, L.A. Schwarz, L. Luo,
    T. Rülicke, S. Hippenmeyer, Cell Reports 35 (2021).
date_created: 2021-06-27T22:01:48Z
date_published: 2021-06-22T00:00:00Z
date_updated: 2023-08-10T13:55:00Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
- _id: PreCl
doi: 10.1016/j.celrep.2021.109274
ec_funded: 1
external_id:
  isi:
  - '000664463600016'
file:
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has_accepted_license: '1'
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language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
project:
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular Mechanisms of Radial Neuronal Migration
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '618444'
  name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 260018B0-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '725780'
  name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Cell Reports
publication_identifier:
  eissn:
  - '22111247'
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/boost-for-mouse-genetic-analysis/
scopus_import: '1'
status: public
title: A genome-wide library of MADM mice for single-cell genetic mosaic analysis
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 35
year: '2021'
...
---
_id: '9793'
abstract:
- lang: eng
  text: Astrocytes extensively infiltrate the neuropil to regulate critical aspects
    of synaptic development and function. This process is regulated by transcellular
    interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes
    coordinate developmental processes among one another to parse out the synaptic
    neuropil and form non-overlapping territories is unknown. Here we identify a molecular
    mechanism regulating astrocyte-astrocyte interactions during development to coordinate
    astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked,
    astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for
    territory and morphological complexity in the developing mouse cortex. Furthermore,
    conditional deletion of Hepacam from developing astrocytes significantly impairs
    gap junction coupling between astrocytes and disrupts the balance between synaptic
    excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy
    with subcortical cysts in humans. Therefore, our findings suggest that disruption
    of astrocyte self-organization mechanisms could be an underlying cause of neural
    pathology.
acknowledgement: This work was supported by the National Institutes of Health (R01
  DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice
  Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships
  from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer
  lab was supported by the European Research Council (ERC) under the European Union’s
  Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported
  by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke
  Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte
  for assistance with proteomic experiments, and Dr. D. Silver for critical review
  of the manuscript. Cartoon elements of figure panels were created using BioRender.com.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine T.
  full_name: Baldwin, Katherine T.
  last_name: Baldwin
- first_name: Christabel X.
  full_name: Tan, Christabel X.
  last_name: Tan
- first_name: Samuel T.
  full_name: Strader, Samuel T.
  last_name: Strader
- first_name: Changyu
  full_name: Jiang, Changyu
  last_name: Jiang
- first_name: Justin T.
  full_name: Savage, Justin T.
  last_name: Savage
- first_name: Xabier
  full_name: Elorza-Vidal, Xabier
  last_name: Elorza-Vidal
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- 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: Raúl
  full_name: Estévez, Raúl
  last_name: Estévez
- first_name: Ru-Rong
  full_name: Ji, Ru-Rong
  last_name: Ji
- first_name: Cagla
  full_name: Eroglu, Cagla
  last_name: Eroglu
citation:
  ama: Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization
    and coupling. <i>Neuron</i>. 2021;109(15):2427-2442.e10. doi:<a href="https://doi.org/10.1016/j.neuron.2021.05.025">10.1016/j.neuron.2021.05.025</a>
  apa: Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal,
    X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling.
    <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2021.05.025">https://doi.org/10.1016/j.neuron.2021.05.025</a>
  chicago: Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang,
    Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls
    Astrocyte Self-Organization and Coupling.” <i>Neuron</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.neuron.2021.05.025">https://doi.org/10.1016/j.neuron.2021.05.025</a>.
  ieee: K. T. Baldwin <i>et al.</i>, “HepaCAM controls astrocyte self-organization
    and coupling,” <i>Neuron</i>, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021.
  ista: Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras
    X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls
    astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.
  mla: Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization
    and Coupling.” <i>Neuron</i>, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10,
    doi:<a href="https://doi.org/10.1016/j.neuron.2021.05.025">10.1016/j.neuron.2021.05.025</a>.
  short: K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal,
    X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron
    109 (2021) 2427–2442.e10.
date_created: 2021-08-06T09:08:25Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2023-09-27T07:46:09Z
day: '04'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2021.05.025
ec_funded: 1
external_id:
  isi:
  - '000692851900010'
  pmid:
  - '34171291'
intvolume: '       109'
isi: 1
issue: '15'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.neuron.2021.05.025
month: '08'
oa: 1
oa_version: Published Version
page: 2427-2442.e10
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
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: HepaCAM controls astrocyte self-organization and coupling
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 109
year: '2021'
...
---
_id: '7815'
abstract:
- lang: eng
  text: Beginning from a limited pool of progenitors, the mammalian cerebral cortex
    forms highly organized functional neural circuits. However, the underlying cellular
    and molecular mechanisms regulating lineage transitions of neural stem cells (NSCs)
    and eventual production of neurons and glia in the developing neuroepithelium
    remains unclear. Methods to trace NSC division patterns and map the lineage of
    clonally related cells have advanced dramatically. However, many contemporary
    lineage tracing techniques suffer from the lack of cellular resolution of progeny
    cell fate, which is essential for deciphering progenitor cell division patterns.
    Presented is a protocol using mosaic analysis with double markers (MADM) to perform
    in vivo clonal analysis. MADM concomitantly manipulates individual progenitor
    cells and visualizes precise division patterns and lineage progression at unprecedented
    single cell resolution. MADM-based interchromosomal recombination events during
    the G2-X phase of mitosis, together with temporally inducible CreERT2, provide
    exact information on the birth dates of clones and their division patterns. Thus,
    MADM lineage tracing provides unprecedented qualitative and quantitative optical
    readouts of the proliferation mode of stem cell progenitors at the single cell
    level. MADM also allows for examination of the mechanisms and functional requirements
    of candidate genes in NSC lineage progression. This method is unique in that comparative
    analysis of control and mutant subclones can be performed in the same tissue environment
    in vivo. Here, the protocol is described in detail, and experimental paradigms
    to employ MADM for clonal analysis and lineage tracing in the developing cerebral
    cortex are demonstrated. Importantly, this protocol can be adapted to perform
    MADM clonal analysis in any murine stem cell niche, as long as the CreERT2 driver
    is present.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
article_number: e61147
article_processing_charge: No
article_type: original
author:
- first_name: Robert J
  full_name: Beattie, Robert J
  id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
  last_name: Beattie
  orcid: 0000-0002-8483-8753
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Nicole
  full_name: Amberg, Nicole
  id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
  last_name: Amberg
  orcid: 0000-0002-3183-8207
- 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: 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: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
citation:
  ama: Beattie RJ, Streicher C, Amberg N, et al. Lineage tracing and clonal analysis
    in developing cerebral cortex using mosaic analysis with double markers (MADM).
    <i>Journal of Visual Experiments</i>. 2020;(159). doi:<a href="https://doi.org/10.3791/61147">10.3791/61147</a>
  apa: Beattie, R. J., Streicher, C., Amberg, N., Cheung, G. T., Contreras, X., Hansen,
    A. H., &#38; Hippenmeyer, S. (2020). Lineage tracing and clonal analysis in developing
    cerebral cortex using mosaic analysis with double markers (MADM). <i>Journal of
    Visual Experiments</i>. MyJove Corporation. <a href="https://doi.org/10.3791/61147">https://doi.org/10.3791/61147</a>
  chicago: Beattie, Robert J, Carmen Streicher, Nicole Amberg, Giselle T Cheung, Ximena
    Contreras, Andi H Hansen, and Simon Hippenmeyer. “Lineage Tracing and Clonal Analysis
    in Developing Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).”
    <i>Journal of Visual Experiments</i>. MyJove Corporation, 2020. <a href="https://doi.org/10.3791/61147">https://doi.org/10.3791/61147</a>.
  ieee: R. J. Beattie <i>et al.</i>, “Lineage tracing and clonal analysis in developing
    cerebral cortex using mosaic analysis with double markers (MADM),” <i>Journal
    of Visual Experiments</i>, no. 159. MyJove Corporation, 2020.
  ista: Beattie RJ, Streicher C, Amberg N, Cheung GT, Contreras X, Hansen AH, Hippenmeyer
    S. 2020. Lineage tracing and clonal analysis in developing cerebral cortex using
    mosaic analysis with double markers (MADM). Journal of Visual Experiments. (159),
    e61147.
  mla: Beattie, Robert J., et al. “Lineage Tracing and Clonal Analysis in Developing
    Cerebral Cortex Using Mosaic Analysis with Double Markers (MADM).” <i>Journal
    of Visual Experiments</i>, no. 159, e61147, MyJove Corporation, 2020, doi:<a href="https://doi.org/10.3791/61147">10.3791/61147</a>.
  short: R.J. Beattie, C. Streicher, N. Amberg, G.T. Cheung, X. Contreras, A.H. Hansen,
    S. Hippenmeyer, Journal of Visual Experiments (2020).
date_created: 2020-05-11T08:31:20Z
date_published: 2020-05-08T00:00:00Z
date_updated: 2024-03-25T23:30:23Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3791/61147
ec_funded: 1
external_id:
  isi:
  - '000546406600043'
file:
- access_level: open_access
  checksum: 3154ea7f90b9fb45e084cd1c2770597d
  content_type: application/pdf
  creator: rbeattie
  date_created: 2020-05-11T08:28:38Z
  date_updated: 2020-07-14T12:48:03Z
  file_id: '7816'
  file_name: jove-protocol-61147-lineage-tracing-clonal-analysis-developing-cerebral-cortex-using.pdf
  file_size: 1352186
  relation: main_file
file_date_updated: 2020-07-14T12:48:03Z
has_accepted_license: '1'
isi: 1
issue: '159'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: M02416
  name: Molecular Mechanisms Regulating Gliogenesis in the Cerebral Cortex
- _id: 268F8446-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: T0101031
  name: Role of Eed in neural stem cell lineage progression
- _id: 260C2330-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '754411'
  name: ISTplus - Postdoctoral Fellowships
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
  grant_number: '24812'
  name: Molecular Mechanisms of Radial Neuronal Migration
- _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: Journal of Visual Experiments
publication_identifier:
  issn:
  - 1940-087X
publication_status: published
publisher: MyJove Corporation
quality_controlled: '1'
related_material:
  record:
  - id: '7902'
    relation: part_of_dissertation
    status: public
scopus_import: '1'
status: public
title: Lineage tracing and clonal analysis in developing cerebral cortex using mosaic
  analysis with double markers (MADM)
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7902'
abstract:
- lang: eng
  text: "Mosaic genetic analysis has been widely used in different model organisms
    such as the fruit fly to study gene-function in a cell-autonomous or tissue-specific
    fashion. More recently, and less easily conducted, mosaic genetic analysis in
    mice has also been enabled with the ambition to shed light on human gene function
    and disease. These genetic tools are of particular interest, but not restricted
    to, the study of the brain. Notably, the MADM technology offers a genetic approach
    in mice to visualize and concomitantly manipulate small subsets of genetically
    defined cells at a clonal level and single cell resolution. MADM-based analysis
    has already advanced the study of genetic mechanisms regulating brain development
    and is expected that further MADM-based analysis of genetic alterations will continue
    to reveal important insights on the fundamental principles of development and
    disease to potentially assist in the development of new therapies or treatments.\r\nIn
    summary, this work completed and characterized the necessary genome-wide genetic
    tools to perform MADM-based analysis at single cell level of the vast majority
    of mouse genes in virtually any cell type and provided a protocol to perform lineage
    tracing using the novel MADM resource. Importantly, this work also explored and
    revealed novel aspects of biologically relevant events in an in vivo context,
    such as the chromosome-specific bias of chromatid sister segregation pattern,
    the generation of cell-type diversity in the cerebral cortex and in the cerebellum
    and finally, the relevance of the interplay between the cell-autonomous gene function
    and cell-non-autonomous (community) effects in radial glial progenitor lineage
    progression.\r\nThis work provides a foundation and opens the door to further
    elucidating the molecular mechanisms underlying neuronal diversity and astrocyte
    generation."
acknowledged_ssus:
- _id: PreCl
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
citation:
  ama: Contreras X. Genetic dissection of neural development in health and disease
    at single cell resolution. 2020. doi:<a href="https://doi.org/10.15479/AT:ISTA:7902">10.15479/AT:ISTA:7902</a>
  apa: Contreras, X. (2020). <i>Genetic dissection of neural development in health
    and disease at single cell resolution</i>. Institute of Science and Technology
    Austria. <a href="https://doi.org/10.15479/AT:ISTA:7902">https://doi.org/10.15479/AT:ISTA:7902</a>
  chicago: Contreras, Ximena. “Genetic Dissection of Neural Development in Health
    and Disease at Single Cell Resolution.” Institute of Science and Technology Austria,
    2020. <a href="https://doi.org/10.15479/AT:ISTA:7902">https://doi.org/10.15479/AT:ISTA:7902</a>.
  ieee: X. Contreras, “Genetic dissection of neural development in health and disease
    at single cell resolution,” Institute of Science and Technology Austria, 2020.
  ista: Contreras X. 2020. Genetic dissection of neural development in health and
    disease at single cell resolution. Institute of Science and Technology Austria.
  mla: Contreras, Ximena. <i>Genetic Dissection of Neural Development in Health and
    Disease at Single Cell Resolution</i>. Institute of Science and Technology Austria,
    2020, doi:<a href="https://doi.org/10.15479/AT:ISTA:7902">10.15479/AT:ISTA:7902</a>.
  short: X. Contreras, Genetic Dissection of Neural Development in Health and Disease
    at Single Cell Resolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-05-29T08:27:32Z
date_published: 2020-06-05T00:00:00Z
date_updated: 2023-10-18T08:45:16Z
day: '05'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: SiHi
doi: 10.15479/AT:ISTA:7902
ec_funded: 1
file:
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  checksum: 43c172bf006c95b65992d473c7240d13
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: xcontreras
  date_created: 2020-06-05T08:18:08Z
  date_updated: 2021-06-07T22:30:03Z
  embargo_to: open_access
  file_id: '7927'
  file_name: PhDThesis_Contreras.docx
  file_size: 53134142
  relation: source_file
- access_level: open_access
  checksum: addfed9128271be05cae3608e03a6ec0
  content_type: application/pdf
  creator: xcontreras
  date_created: 2020-06-05T08:18:07Z
  date_updated: 2021-06-07T22:30:03Z
  embargo: 2021-06-06
  file_id: '7928'
  file_name: PhDThesis_Contreras.pdf
  file_size: 35117191
  relation: main_file
file_date_updated: 2021-06-07T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: '214'
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_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '6830'
    relation: dissertation_contains
    status: public
  - id: '28'
    relation: dissertation_contains
    status: public
  - id: '7815'
    relation: dissertation_contains
    status: public
status: public
supervisor:
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
title: Genetic dissection of neural development in health and disease at single cell
  resolution
type: dissertation
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '6830'
article_processing_charge: No
article_type: letter_note
author:
- 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
citation:
  ama: Contreras X, Hippenmeyer S. Memo1 tiles the radial glial cell grid. <i>Neuron</i>.
    2019;103(5):750-752. doi:<a href="https://doi.org/10.1016/j.neuron.2019.08.021">10.1016/j.neuron.2019.08.021</a>
  apa: Contreras, X., &#38; Hippenmeyer, S. (2019). Memo1 tiles the radial glial cell
    grid. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2019.08.021">https://doi.org/10.1016/j.neuron.2019.08.021</a>
  chicago: Contreras, Ximena, and Simon Hippenmeyer. “Memo1 Tiles the Radial Glial
    Cell Grid.” <i>Neuron</i>. Elsevier, 2019. <a href="https://doi.org/10.1016/j.neuron.2019.08.021">https://doi.org/10.1016/j.neuron.2019.08.021</a>.
  ieee: X. Contreras and S. Hippenmeyer, “Memo1 tiles the radial glial cell grid,”
    <i>Neuron</i>, vol. 103, no. 5. Elsevier, pp. 750–752, 2019.
  ista: Contreras X, Hippenmeyer S. 2019. Memo1 tiles the radial glial cell grid.
    Neuron. 103(5), 750–752.
  mla: Contreras, Ximena, and Simon Hippenmeyer. “Memo1 Tiles the Radial Glial Cell
    Grid.” <i>Neuron</i>, vol. 103, no. 5, Elsevier, 2019, pp. 750–52, doi:<a href="https://doi.org/10.1016/j.neuron.2019.08.021">10.1016/j.neuron.2019.08.021</a>.
  short: X. Contreras, S. Hippenmeyer, Neuron 103 (2019) 750–752.
date_created: 2019-08-25T22:00:50Z
date_published: 2019-09-04T00:00:00Z
date_updated: 2024-03-25T23:30:23Z
day: '04'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2019.08.021
external_id:
  isi:
  - '000484400200002'
  pmid:
  - '31487522'
intvolume: '       103'
isi: 1
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.neuron.2019.08.021
month: '09'
oa: 1
oa_version: Published Version
page: 750-752
pmid: 1
publication: Neuron
publication_identifier:
  eissn:
  - '10974199'
  issn:
  - '08966273'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '7902'
    relation: part_of_dissertation
    status: public
scopus_import: '1'
status: public
title: Memo1 tiles the radial glial cell grid
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 103
year: '2019'
...
---
_id: '28'
abstract:
- lang: eng
  text: 'This scientific commentary refers to ‘NEGR1 and FGFR2 cooperatively regulate
    cortical development and core behaviours related to autism disorders in mice’
    by Szczurkowska et al. '
article_processing_charge: No
author:
- 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
citation:
  ama: Contreras X, Hippenmeyer S. Incorrect trafficking route leads to autism. <i>Brain
    a journal of neurology</i>. 2018;141(9):2542-2544. doi:<a href="https://doi.org/10.1093/brain/awy218">10.1093/brain/awy218</a>
  apa: Contreras, X., &#38; Hippenmeyer, S. (2018). Incorrect trafficking route leads
    to autism. <i>Brain a Journal of Neurology</i>. Oxford University Press. <a href="https://doi.org/10.1093/brain/awy218">https://doi.org/10.1093/brain/awy218</a>
  chicago: Contreras, Ximena, and Simon Hippenmeyer. “Incorrect Trafficking Route
    Leads to Autism.” <i>Brain a Journal of Neurology</i>. Oxford University Press,
    2018. <a href="https://doi.org/10.1093/brain/awy218">https://doi.org/10.1093/brain/awy218</a>.
  ieee: X. Contreras and S. Hippenmeyer, “Incorrect trafficking route leads to autism,”
    <i>Brain a journal of neurology</i>, vol. 141, no. 9. Oxford University Press,
    pp. 2542–2544, 2018.
  ista: Contreras X, Hippenmeyer S. 2018. Incorrect trafficking route leads to autism.
    Brain a journal of neurology. 141(9), 2542–2544.
  mla: Contreras, Ximena, and Simon Hippenmeyer. “Incorrect Trafficking Route Leads
    to Autism.” <i>Brain a Journal of Neurology</i>, vol. 141, no. 9, Oxford University
    Press, 2018, pp. 2542–44, doi:<a href="https://doi.org/10.1093/brain/awy218">10.1093/brain/awy218</a>.
  short: X. Contreras, S. Hippenmeyer, Brain a Journal of Neurology 141 (2018) 2542–2544.
date_created: 2018-12-11T11:44:14Z
date_published: 2018-09-01T00:00:00Z
date_updated: 2024-03-25T23:30:23Z
day: '01'
department:
- _id: SiHi
doi: 10.1093/brain/awy218
external_id:
  isi:
  - '000446548100012'
intvolume: '       141'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa_version: None
page: 2542 - 2544
publication: Brain a journal of neurology
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
  record:
  - id: '7902'
    relation: part_of_dissertation
    status: public
scopus_import: '1'
status: public
title: Incorrect trafficking route leads to autism
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 141
year: '2018'
...
---
_id: '3'
abstract:
- lang: eng
  text: SETD5 gene mutations have been identified as a frequent cause of idiopathic
    intellectual disability. Here we show that Setd5-haploinsufficient mice present
    developmental defects such as abnormal brain-to-body weight ratios and neural
    crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments
    in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile
    of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are
    accompanied by abnormal expression of postsynaptic density proteins previously
    associated with cognition. Our data additionally indicate that Setd5 regulates
    RNA polymerase II dynamics and gene transcription via its interaction with the
    Hdac3 and Paf1 complexes, findings potentially explaining the gene expression
    defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive
    role of Setd5 in a biological pathway found to be disrupted in humans with intellectual
    disability and autism spectrum disorder.
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
acknowledgement: This work was supported by the Simons Foundation Autism Research
  Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.
article_processing_charge: No
article_type: original
author:
- first_name: Elena
  full_name: Deliu, Elena
  id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
  last_name: Deliu
  orcid: 0000-0002-7370-5293
- first_name: Niccoló
  full_name: Arecco, Niccoló
  last_name: Arecco
- first_name: Jasmin
  full_name: Morandell, Jasmin
  id: 4739D480-F248-11E8-B48F-1D18A9856A87
  last_name: Morandell
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Ximena
  full_name: Contreras, Ximena
  id: 475990FE-F248-11E8-B48F-1D18A9856A87
  last_name: Contreras
- first_name: Charles
  full_name: Girardot, Charles
  last_name: Girardot
- first_name: Eva
  full_name: Käsper, Eva
  last_name: Käsper
- first_name: Alena
  full_name: Kozlova, Alena
  id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D
  last_name: Kozlova
- first_name: Kasumi
  full_name: Kishi, Kasumi
  id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
  last_name: Kishi
- first_name: Ilaria
  full_name: Chiaradia, Ilaria
  id: B6467F20-02D0-11E9-BDA5-E960C241894A
  last_name: Chiaradia
  orcid: 0000-0002-9529-4464
- first_name: Kyung
  full_name: Noh, Kyung
  last_name: Noh
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual
    disability gene SETD5 disturbs developmental gene expression and cognition. <i>Nature
    Neuroscience</i>. 2018;21(12):1717-1727. doi:<a href="https://doi.org/10.1038/s41593-018-0266-2">10.1038/s41593-018-0266-2</a>
  apa: Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot,
    C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene
    SETD5 disturbs developmental gene expression and cognition. <i>Nature Neuroscience</i>.
    Nature Publishing Group. <a href="https://doi.org/10.1038/s41593-018-0266-2">https://doi.org/10.1038/s41593-018-0266-2</a>
  chicago: Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena
    Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual
    Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” <i>Nature
    Neuroscience</i>. Nature Publishing Group, 2018. <a href="https://doi.org/10.1038/s41593-018-0266-2">https://doi.org/10.1038/s41593-018-0266-2</a>.
  ieee: E. Deliu <i>et al.</i>, “Haploinsufficiency of the intellectual disability
    gene SETD5 disturbs developmental gene expression and cognition,” <i>Nature Neuroscience</i>,
    vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.
  ista: Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper
    E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency
    of the intellectual disability gene SETD5 disturbs developmental gene expression
    and cognition. Nature Neuroscience. 21(12), 1717–1727.
  mla: Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene
    SETD5 Disturbs Developmental Gene Expression and Cognition.” <i>Nature Neuroscience</i>,
    vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:<a href="https://doi.org/10.1038/s41593-018-0266-2">10.1038/s41593-018-0266-2</a>.
  short: E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot,
    E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience
    21 (2018) 1717–1727.
date_created: 2018-12-11T11:44:05Z
date_published: 2018-11-19T00:00:00Z
date_updated: 2024-03-25T23:30:25Z
day: '19'
ddc:
- '570'
department:
- _id: GaNo
- _id: EdHa
doi: 10.1038/s41593-018-0266-2
external_id:
  isi:
  - '000451324700010'
file:
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  checksum: 60abd0f05b7cdc08a6b0ec460884084f
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  creator: dernst
  date_created: 2019-04-09T07:41:57Z
  date_updated: 2020-07-14T12:45:58Z
  file_id: '6255'
  file_name: 2017_NatureNeuroscience_Deliu.pdf
  file_size: 8167169
  relation: main_file
file_date_updated: 2020-07-14T12:45:58Z
has_accepted_license: '1'
intvolume: '        21'
isi: 1
issue: '12'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: 1717 - 1727
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
  grant_number: '401299'
  name: Probing development and reversibility of autism spectrum disorders
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '8054'
pubrep_id: '1071'
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/
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scopus_import: '1'
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title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental
  gene expression and cognition
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 21
year: '2018'
...
