Molecular machinery governing GABAergic neuron specification in the cerebellum

Although the cerebellum contains a relatively small variety of neurons, the molecular machinery governing neuronal generation and/or subtype specification is still poorly understood. We identified a novel mutant mouse, cerebelless, which lacks the entire cerebellar cortex but survives up to the adult stages. Analyses of its phenotypes and identification of its responsible gene clarified that Prf1a (pancreas transcription factor 1a), which encodes a bHLH transcription factor, is involved in cerebellar GABAergic neuron production. Together with recently published papers describing another bHLH gene, Math1, our study proposes that two bHLH transcription factors, PTF1A and MATH1, may participate in regionalization of cerebellar neuroepithelium, defining two distinct areas, the ventricular zone and the rhombic lip, which generate GABAergic and glutamatergic neurons, respectively. Here I will describe a novel cerebellar mutant, cerebelless, review the role of Ptf1a in GABAergic neuron production, and discuss new insights into cerebellar development from the vantage point of regulation by bHLH transcription factors.