Ptf1a, a bHLH Transcriptional Gene, Defines GABAergic Neuronal Fates in Cerebellum

• DOI: 10.1016/j.neuron.2005.06.007
• Publication Date: 2005-07-26T19:08:29Z
• Authors: Mikio Hoshino; Shoko Nakamura; Kiyoshi Mori; Takeshi Kawauchi; Mami Terao; Yoshiaki V. Nishi...; Akihisa Fukuda; Toshimitsu Fuse; Naoki Matsuo; Masaki Sone; Masahiko Watanabe; Haruhiko Bito; Toshio Terashima; Christopher V.E. ...; Yoshiya Kawaguchi; Kazuwa Nakao; Yo-ichi Nabeshima
• Keywords: Calbindins; 0303 health sciences; Cell Death; Neuroscience(all); Green Fluorescent Proteins; Helix-Loop-Helix Motifs; Age Factors; Gene Expression Regulation, Developmental; Cell Count; Cell Differentiation; In Vitro Techniques; Embryo, Mammalian; Immunohistochemistry; 03 medical and health sciences; Animals, Newborn; Bromodeoxyuridine; Calbindin 2; Cerebellum; Glial Fibrillary Acidic Protein; In Situ Nick-End Labeling; Animals; In Situ Hybridization, Fluorescence; Cell Size

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.