---
_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: 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
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  file_name: 2021_CellReports_Zhang.pdf
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file_date_updated: 2021-06-15T14:01:35Z
has_accepted_license: '1'
intvolume: '        35'
isi: 1
issue: '10'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
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'
...