Heterotrimeric G proteins regulate daughter cell size asymmetry in Drosophila neuroblast divisions
Heterotrimeric G proteins regulate daughter cell size asymmetry in Drosophila neuroblast divisions
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DOI：
10.1016/s0960-9822(03)00334-8
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发表时间：
2003-05-27
期刊：
影响因子：
9.2
通讯作者：
Matsuzaki, F
中科院分区：
文献类型：
--
作者：
Fuse, N;Hisata, K;Matsuzaki, F
分裂通常通过偏离中心的分裂产生大小不等的子细胞，这是由于有丝分裂纺锤体的移位或它们的不对称性。果蝇神经母细胞主要使用后一种机制分裂成一个大的顶端神经母细胞和一个小的基底神经节母细胞（GMC），其中神经命运决定因素分离。顶端本地化的组件调节纺锤体的不对称性和本地化的决定因素。在这里，我们表明，不对称纺锤体的形成依赖于异源三聚体G蛋白的GP亚基介导的信号传导。Gbeta 13 F分布在整个神经母细胞皮层。它的缺乏诱导一个大的对称纺锤体，并导致分裂成几乎相等大小的细胞与正常分离的决定因素。相反，升高的Gbeta 13 F活性产生一个小的纺锤体，这表明该因子抑制纺锤体的发育。顶端成分的消耗也导致在中期形成一个小的对称纺锤体。因此，顶端组分和Gbeta 13 F相反地影响有丝分裂纺锤体的形状。我们建议，差异激活GP信号偏向纺锤体发育成神经细胞，从而导致不对称的纺锤体。此外，GP突变神经母细胞的多个相等的分裂伴随神经缺陷;这一发现表明偏心分裂在确保神经母细胞的干细胞特性中不可或缺的作用。
division often generates unequally sized daughter cells by off-center cleavages, which are due to either displacement of mitotic spindles or their asymmetry. Drosophila neuroblasts predominantly use the latter mechanism to divide into a large apical neuroblast and a small basal ganglion mother cell (GMC), where the neural fate determinants segregate. Apically localized components regulate both the spindle asymmetry and the localization of the determinants. Here, we show that asymmetric spindle formation depends on signaling mediated by the GP subunit of heterotrimeric G proteins. Gbeta13F distributes throughout the neuroblast cortex. Its lack induces a large symmetric spindle and causes division into nearly equal-sized cells with normal segregation of the determinants. In contrast, elevated Gbeta13F activity generates a small spindle, suggesting that this factor suppresses spindle development. Depletion of the apical components also results in the formation of a small symmetric spindle at metaphase. Therefore, the apical components and Gbeta13F affect the mitotic spindle shape oppositely. We propose that differential activation of GP signaling biases spindle development within neuroblasts and thereby causes asymmetric spindles. Furthermore, the multiple equal cleavages of GP mutant neuroblasts accompany neural defects; this finding suggests indispensable roles of eccentric division in assuring the stem cell properties of neuroblasts.