title: Astroglial cells in the external granular layer are precursors of cerebellar granule neurons in neonates.
abstract: It is well established that cerebellar granule cell precursors (GCPs) initially derive from progenitors in the rhombic lip of the embryonic cerebellar primordium. GCPs proliferate and migrate tangentially across the cerebellum to form the external granule cell layer (EGL) in late embryogenesis and early postnatal development. It is unclear whether GCPs are specified exclusively in the embryonic rhombic lip or whether their precursor persists in the neonate. Using transgenic mice expressing DsRed under the human glial fibrillary acidic protein (hGFAP) promoter, we found 2 populations of DsRed(+) cells in the EGL in the first postnatal week defined by bright and faint DsRed-fluorescent signal. Bright DsRed(+) cells have a protein expression profile and electrophysiological characteristics typical of astrocytes, but faint DsRed(+) cells in the EGL and internal granule cell layer (IGL) express markers and physiological properties of immature neurons. To determine if these astroglial cells gave rise to GCPs, we genetically tagged them with EGFP or betagal reporter genes at postnatal day (P)3-P5 using a hGFAP promoter driven inducible Cre recombinase. We found that GFAP promoter(+) cells in the EGL are proliferative and express glial and neural stem cell markers. In addition, immature granule cells (GCs) en route to the IGL at P12 as well as GCs in the mature cerebellum, 30days after recombination, express the reporter protein, suggesting that GFAP promoter(+) cells in the EGL generate a subset of granule cells. The identification of glial cells which function as neuronal progenitor cells profoundly impacts our understanding of cellular plasticity in the developing cerebellum.
authors.affiliation: Child Study Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: John
authors.initials: J
authors.lastname: Silbereis
authors.forename: Tristan
authors.initials: T
authors.lastname: Heintz
authors.forename: Mary Morgan
authors.initials: MM
authors.lastname: Taylor
authors.forename: Yosif
authors.initials: Y
authors.lastname: Ganat
authors.forename: Laura R
authors.initials: LR
authors.lastname: Ment
authors.forename: Angelique
authors.initials: A
authors.lastname: Bordey
authors.forename: Flora
authors.initials: F
authors.lastname: Vaccarino
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000276:immunology; D019070:Cell Lineage / Q000502:physiology; D002531:Cerebellum / Q000166:cytology*; D017930:Genes, Reporter; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D019426:Integrases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D001616:beta-Galactosidase
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D019426:Integrases; D001616:beta-Galactosidase; C500943:Atoh1 protein, mouse; C485184:enhanced green fluorescent protein; C045073:Cre recombinase
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