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

      Neuron

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

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          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.

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          Journal
          10.1016/j.neuron.2005.06.007
          16039563

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