Hoshino Mikio
Department of Pathology and Tumor Biology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan.
Cerebellum. 2006;5(3):193-8. doi: 10.1080/14734220600589202.
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 Ptf1a (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.
尽管小脑包含的神经元种类相对较少，但调控神经元生成和/或亚型特化的分子机制仍未得到充分了解。我们鉴定出一种新型突变小鼠——无小脑小鼠，它缺乏整个小脑皮质，但能存活至成年阶段。对其表型的分析以及对其致病基因的鉴定表明，编码bHLH转录因子的Ptf1a（胰腺转录因子1a）参与了小脑GABA能神经元的产生。结合最近发表的描述另一个bHLH基因Math1的论文，我们的研究提出，两个bHLH转录因子PTF1A和MATH1可能参与小脑神经上皮的区域化，定义了两个不同的区域，即脑室区和菱唇，它们分别产生GABA能神经元和谷氨酸能神经元。在此，我将描述一种新型小脑突变体——无小脑小鼠，回顾Ptf1a在GABA能神经元产生中的作用，并从bHLH转录因子调控的角度讨论对小脑发育的新见解。
