Ben-Arie N, Bellen H J, Armstrong D L, McCall A E, Gordadze P R, Guo Q, Matzuk M M, Zoghbi H Y
Department of Molecular and Human Genetics, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
Nature. 1997 Nov 13;390(6656):169-72. doi: 10.1038/36579.
The cerebellum is essential for fine motor control of movement and posture, and its dysfunction disrupts balance and impairs control of speech, limb and eye movements. The developing cerebellum consists mainly of three types of neuronal cells: granule cells in the external germinal layer, Purkinje cells, and neurons of the deep nuclei. The molecular mechanisms that underlie the specific determination and the differentiation of each of these neuronal subtypes are unknown. Math1, the mouse homologue of the Drosophila gene atonal, encodes a basic helix-loop-helix transcription factor that is specifically expressed in the precursors of the external germinal layer and their derivatives. Here we report that mice lacking Math1 fail to form granule cells and are born with a cerebellum that is devoid of an external germinal layer. To our knowledge, Math1 is the first gene to be shown to be required in vivo for the genesis of granule cells, and hence the predominant neuronal population in the cerebellum.
小脑对于运动和姿势的精细运动控制至关重要，其功能障碍会破坏平衡并损害言语、肢体和眼球运动的控制。发育中的小脑主要由三种类型的神经元细胞组成：外颗粒层中的颗粒细胞、浦肯野细胞和深部核团的神经元。这些神经元亚型各自特定的决定和分化所依据的分子机制尚不清楚。Math1是果蝇无调性基因的小鼠同源物，编码一种碱性螺旋-环-螺旋转录因子，该因子在外颗粒层及其衍生物的前体细胞中特异性表达。在此我们报告，缺乏Math1的小鼠无法形成颗粒细胞，出生时小脑没有外颗粒层。据我们所知，Math1是第一个被证明在体内对于颗粒细胞（即小脑中主要的神经元群体）的发生是必需的基因。
