Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum

Zhang, Tingting; Liu, Tengyuan; Mora, Natalia; Guegan, Justine; Bertrand, Mathilde; Contreras, Ximena; Hansen, Andi H; Streicher, Carmen; Anderle, Marica; Danda, Natasha; Tiberi, Luca; Hippenmeyer, Simon; Hassan, Bassem A.

Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum

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.

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DOI

10.1016/j.celrep.2021.109208

Journal Article | Published | English

Scopus indexed

Author

Zhang, Tingting; Liu, Tengyuan; Mora, Natalia; Guegan, Justine; Bertrand, Mathilde; Contreras Paniagua, Ximena^ISTA; Hansen, Andi H^ISTA; Streicher, Carmen^ISTA; Anderle, Marica; Danda, Natasha; Tiberi, Luca; Hippenmeyer, Simon^ISTA
All

Department

Hippenmeyer Group

Grant

Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
Molecular Mechanisms of Radial Neuronal Migration

Abstract

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.

Publishing Year

2021

Date Published

2021-06-08

Journal Title

Cell Reports

Publisher

Elsevier

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 .

Volume

Issue

Article Number

109208

eISSN

22111247

IST-REx-ID

8546

Cite this

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

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

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.

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.

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.

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