1. Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum
- Author
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Andi H. Hansen, Natalia Mora, Natalia Danda, Justine Guegan, Luca Tiberi, Simon Hippenmeyer, Mathilde Bertrand, Marica Anderle, Tingting Zhang, Carmen Streicher, Tengyuan Liu, Ximena Contreras, Bassem A. Hassan, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Institute of Science and Technology [Austria] (IST Austria), University of Trento [Trento], HAL-SU, Gestionnaire, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Institute of Science and Technology [Klosterneuburg, Austria] (IST Austria)
- Subjects
0301 basic medicine ,DOUBLE MARKERS ,EXPRESSION ,Cerebellum ,GLIOGENESIS ,MOSAIC ANALYSIS ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Notch signaling pathway ,Biology ,Cell fate determination ,Inhibitory postsynaptic potential ,General Biochemistry, Genetics and Molecular Biology ,NEUROGENESIS ,03 medical and health sciences ,0302 clinical medicine ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,medicine ,Humans ,human cerebellar organoids ,SPECIFICATION ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,Notch signaling ,030304 developmental biology ,Progenitor ,neural stem cells ,Neurons ,0303 health sciences ,Science & Technology ,Receptors, Notch ,Neurogenesis ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Cell Differentiation ,neuronal diversity ,Cell Biology ,STEM ,Embryonic stem cell ,mouse cerebellum ,Neural stem cell ,030104 developmental biology ,medicine.anatomical_structure ,DIFFERENTIATION ,MEDULLOBLASTOMA ,Excitatory postsynaptic potential ,Neuroscience ,Life Sciences & Biomedicine ,INTEGRATION ,030217 neurology & neurosurgery - Abstract
SUMMARYBrain neurons arise from relatively few progenitors capable of giving rise to an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis in both the cortex and the cerebellum is that excitatory neurons and inhibitory neurons derive from separate, spatially segregated, progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both excitatory and inhibitory lineages exist and how such a fate decision may be regulated is unknown. Using cerebellar development as a model, we discover that individual embryonic cerebellar progenitors give rise to both inhibitory and excitatory lineages. We find that gradations of Notch activity levels determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate. Daughters with intermediate levels of Notch activity become fate restricted to generate inhibitory neurons, while 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.Graphical summary
- Published
- 2021