SMAD4 is essential for generating subtypes of neurons during cerebellar development

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• 作者：Marie Fernandes ; Michelle Antoine ; Jean M. Hé ; bert ; ^{jean.hebert@einstein.yu.edu}
• 关键词：SMAD4 ; Rhombic lip ; Granule cell precursor ; Deep cerebellar nuclei ; Unipolar brush cells ; Mouse
• 刊名：Developmental Biology
• 出版年：2012
• 期刊代码：167_00121606
• 类别：bio
• 出版时间：1 May, 2012
• 卷：365
• 期：1
• 页码：82-90
• 文件大小：3384 K

摘要

Cerebellum development involves the coordinated production of multiple neuronal cell types. The cerebellar primordium contains two germinative zones, the rhombic lip (RL) and the ventricular zone (VZ), which generate different types of glutamatergic and GABAergic neurons, respectively. What regulates the specification and production of glutamatergic and GABAergic neurons as well as the subtypes for each of these two broad classes remains largely unknown. Here we demonstrate with conditional genetic approaches in mice that SMAD4, a major mediator of BMP and TGF尾 signaling, is required early in cerebellar development for maintaining the RL and generating subsets of RL-derived glutamatergic neurons, namely neurons of the deep cerebellar nuclei, unipolar brush cells, and the late cohort of granule cell precursors (GCPs). The early cohort of GCPs, despite being deficient for SMAD4, is still generated. In addition, the numbers of GABAergic neurons are reduced in the mutant and the distribution of Purkinje cells becomes abnormal. These studies demonstrate a temporally and spatially restricted requirement for SMAD4 in generating subtypes of cerebellar neurons.