title: Origins and control of the differentiation of inhibitory interneurons and glia in the cerebellum.
abstract: Cerebellar GABAergic interneurons and glia originate from progenitors that delaminate from the ventricular neuroepithelium and proliferate in the prospective white matter. Even though this population of progenitor cells is multipotent as a whole, clonal analysis indicates that different lineages are already separated during postnatal development and little is known about the mechanisms that regulate the specification and differentiation of these cerebellar types at earlier stages. Here, we investigate the role of Ascl1 in the development of inhibitory interneurons and glial cells in the cerebellum. This gene is expressed by maturing oligodendrocytes and GABAergic interneurons and is required for the production of appropriate quantities of these cells, which are severely reduced in Ascl1(-/-) mouse cerebella. Nevertheless, the two lineages are not related and the majority of oligodendrocytes populating the developing cerebellum actually derive from extracerebellar sources. Targeted electroporation of Ascl1-expression vectors to ventricular neuroepithelium progenitors enhances the production of interneurons and completely suppresses astrocytic differentiation, whereas loss of Ascl1 function has opposite effects on both cell types. Our results indicate that Ascl1 directs ventricular neuroepithelium progenitors towards inhibitory interneuron fate and restricts their ability to differentiate along the astroglial lineage.
authors.affiliation: CNRS UMR 8542, Biology Department, Ecole Normale Supérieure, 46 Rue d'Ulm, 75005 Paris, France.
authors.forename: Piercesare
authors.initials: P
authors.lastname: Grimaldi
authors.forename: Carlos
authors.initials: C
authors.lastname: Parras
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
authors.forename: Marion
authors.initials: M
authors.lastname: Wassef
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D002531:Cerebellum / Q000166:cytology* / Q000196:embryology; D007395:Interneurons / Q000166:cytology* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C499317:Ascl1 protein, mouse