Sanada Kamon, Tsai Li-Huei
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Cell. 2005 Jul 15;122(1):119-31. doi: 10.1016/j.cell.2005.05.009.
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.
发育中的哺乳动物大脑中的神经元由增殖性脑室区的祖细胞产生，在神经发生过程中，祖细胞分裂的控制对于产生正确数量的神经元至关重要。在此，我们证实异源三聚体G蛋白的Gβγ亚基是发育中的新皮质中神经祖细胞正确的有丝分裂纺锤体定向所必需的。干扰祖细胞中的Gβγ功能会导致纺锤体定向从顶-基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了神经命运，而不是正常的不对称细胞命运。沉默AGS3（一种Gβγ的非受体激活剂）会导致与Gβγ受损类似的缺陷，这表明祖细胞中的AGS3-Gβγ信号传导调节顶-基分裂和不对称细胞命运决定。此外，我们的观察结果表明，子细胞的细胞命运决定与祖细胞中的有丝分裂纺锤体定向相关联。
