title: Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum.
abstract: The molecular machinery governing glutamatergic-GABAergic neuronal subtype specification is unclear. Here we describe a cerebellar mutant, cerebelless, which lacks the entire cerebellar cortex in adults. The primary defect of the mutant brains was a specific inhibition of GABAergic neuron production from the cerebellar ventricular zone (VZ), resulting in secondary and complete loss of external germinal layer, pontine, and olivary nuclei during development. We identified the responsible gene, Ptf1a, whose expression was lost in the cerebellar VZ but was maintained in the pancreas in cerebelless. Lineage tracing revealed that two types of neural precursors exist in the cerebellar VZ: Ptf1a-expressing and -nonexpressing precursors, which generate GABAergic and glutamatergic neurons, respectively. Introduction of Ptf1a into glutamatergic neuron precursors in the dorsal telencephalon generated GABAergic neurons with representative morphological and migratory features. Our results suggest that Ptf1a is involved in driving neural precursors to differentiate into GABAergic neurons in the cerebellum.
authors.affiliation: Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. mikio@lmls.med.kyoto-u.ac.jp
authors.forename: Mikio
authors.initials: M
authors.lastname: Hoshino
authors.forename: Shoko
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawauchi
authors.forename: Mami
authors.initials: M
authors.lastname: Terao
authors.forename: Yoshiaki V
authors.initials: YV
authors.lastname: Nishimura
authors.forename: Akihisa
authors.initials: A
authors.lastname: Fukuda
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fuse
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsuo
authors.forename: Masaki
authors.initials: M
authors.lastname: Sone
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
authors.forename: Toshio
authors.initials: T
authors.lastname: Terashima
authors.forename: Christopher V E
authors.initials: CV
authors.lastname: Wright
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
authors.forename: Yo-Ichi
authors.initials: Y
authors.lastname: Nabeshima
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D064032:Calbindin 2; D064026:Calbindins; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D048429:Cell Size; D002531:Cerebellum / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins; D018257:Helix-Loop-Helix Motifs / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D008959:Models, Neurological; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009474:Neurons / Q000145:classification / Q000502:physiology*; D019696:Peptidylprolyl Isomerase / Q000502:physiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D064032:Calbindin 2; D064026:Calbindins; D005904:Glial Fibrillary Acidic Protein; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D001616:beta-Galactosidase; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse; D001973:Bromodeoxyuridine