Ptf1a, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum.

Hoshino M, Nakamura S, Mori K, Kawauchi T, Terao M, Nishimura YV, Fukuda A, Fuse T, Matsuo N, Sone M, Watanabe M, Bito H, Terashima T, Wright CV, Kawaguchi Y, Nakao K, Nabeshima Y
Neuron. 2005 47 (2): 201-13

PMID: 16039563 · DOI:10.1016/j.neuron.2005.06.007

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.

MeSH Terms (32)

Age Factors Animals Animals, Newborn beta-Galactosidase Bromodeoxyuridine Calbindin 2 Calbindins Cell Count Cell Death Cell Differentiation Cell Size Cerebellum Embryo, Mammalian gamma-Aminobutyric Acid Gene Expression Regulation, Developmental Glial Fibrillary Acidic Protein Green Fluorescent Proteins Helix-Loop-Helix Motifs Immunohistochemistry In Situ Hybridization, Fluorescence In Situ Nick-End Labeling In Vitro Techniques Mice Mice, Mutant Strains Models, Neurological Neurons NIMA-Interacting Peptidylprolyl Isomerase Peptidylprolyl Isomerase Phenotype Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger S100 Calcium Binding Protein G

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