SMAD4 is essential for generating subtypes of neurons during cerebellar development.
SMAD4 is essential for generating subtypes of neurons during cerebellar development.
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DOI：
10.1016/j.ydbio.2012.02.017
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发表时间：
2012-05-01
影响因子：
2.7
通讯作者：
Hébert JM
中科院分区：
文献类型：
--
作者：
Fernandes M;Antoine M;Hébert JM
小脑的发育涉及多种神经元细胞类型的协调生产。小脑原基包含两个萌发区：菱形唇区（RL）和心室区（VZ），分别产生不同类型的谷氨酸能神经元和gaba能神经元。是什么调控谷氨酸能和gaba能神经元的规格和产生，以及这两大类神经元的亚型在很大程度上仍然未知。在这里，我们通过条件遗传方法在小鼠中证明SMAD4， BMP和TGFβ信号的主要介质，在小脑发育早期需要维持RL和产生RL来源的谷氨酸能神经元亚群，即小脑深部核神经元，单极刷细胞和晚期颗粒细胞前体（GCPs）。尽管缺乏SMAD4，早期的gcp群体仍然会产生。突变体gaba能神经元数量减少，浦肯野细胞分布异常。这些研究表明，在产生小脑神经元亚型时，SMAD4的需求在时间和空间上受到限制。
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 the 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 TGFβ 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, are 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.
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