G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors.
G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors.
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作者：
K. Sanada;L. Tsai
发育中的哺乳动物大脑中的神经元是由增殖性脑室区的祖细胞产生的，祖细胞分裂的控制对于在神经发生过程中产生正确数量的神经元至关重要。在这里，我们确定异源三聚体 G 蛋白的 Gbetagamma 亚基是发育中新皮质中神经祖细胞正确有丝分裂纺锤体方向所必需的。干扰祖细胞中的 Gbetagamma 功能会导致纺锤体方向从顶底分裂转变为平面分裂。这导致祖细胞过度分化为神经元，因为两个子细胞都采用神经命运而不是正常的不对称细胞命运。沉默 AGS3（Gbetagamma 的非受体激活剂）会导致与 Gbetagamma 损伤类似的缺陷，这提供了祖细胞中 AGS3-Gbetagamma 信号传导调节顶端-基底分裂和不对称细胞命运决定的证据。此外，我们的观察表明，子细胞的细胞命运决定与祖细胞的有丝分裂纺锤体方向相关。
Neurons in the developing mammalian brain are generated from progenitor cells in the proliferative ventricular zone, and control of progenitor division is essential to produce the correct number of neurons during neurogenesis. Here we establish that Gbetagamma subunits of heterotrimeric G proteins are required for proper mitotic-spindle orientation of neural progenitors in the developing neocortex. Interfering with Gbetagamma function in progenitors causes a shift in spindle orientation from apical-basal divisions to planar divisions. This results in hyperdifferentiation of progenitors into neurons as a consequence of both daughter cells adopting a neural fate instead of the normal asymmetric cell fates. Silencing AGS3, a nonreceptor activator of Gbetagamma, results in defects similar to the impairment of Gbetagamma, providing evidence that AGS3-Gbetagamma signaling in progenitors regulates apical-basal division and asymmetric cell-fate decisions. Furthermore, our observations indicate that the cell-fate decision of daughter cells is coupled to mitotic-spindle orientation in progenitors.