Spindle Orientation-Independent Control of Cell Fate Determination by RGS3 and KIF20A.
Spindle Orientation-Independent Control of Cell Fate Determination by RGS3 and KIF20A.
复制标题
RGS3 和 KIF20A 对细胞命运决定的主轴方向独立控制。
DOI：
10.1093/texcom/tgaa003
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发表时间：
2020
影响因子：
--
通讯作者：
Lu,Qiang
中科院分区：
文献类型：
--
作者：
Qiu,Runxiang;Murai,Kiyohito;Lu,Qiang
有人提出，类似于其在无脊椎动物神经系统中的作用，分裂的神经祖细胞的有丝分裂纺锤体方向（或细胞分裂平面方向）指定哺乳动物脑中子细胞的命运，在神经发生过程中通过对称与不对称的细胞分裂调节神经元的产生。纺锤体/卵裂平面方向在哺乳动物细胞命运决定中的充分性的实验测试产生了相互矛盾的结果。另一方面，在哺乳动物细胞命运决定中纺锤体/切割平面取向的必要性尚未得到解决。在这里，我们研究了在RGS 3-KIF 20 A相互作用轴功能丧失的小鼠中皮质神经发生过程中纺锤体/卵裂平面取向的必要性。我们提出的证据表明，虽然RGS 3或KIF 20 A的失活与神经祖细胞从增殖到分化分裂的转变有关，但这些基因突变并没有导致纺锤体/卵裂平面方向的预期改变。我们的研究结果表明，RGS 3-KIF 20 A轴调节哺乳动物皮质的增殖和分化之间的平衡，采用一种独立于纺锤体/卵裂平面方向的机制。这些数据还警告不要使用纺锤体/切割平面取向作为细胞命运确定的同义词。
It was proposed that similar to its role in the invertebrate nervous system, mitotic spindle orientation (or cell cleavage plane orientation) of a dividing neural progenitor cell specifies the fate of daughter cells in the mammalian brain, modulating the production of neurons via symmetric versus asymmetric cell divisions during the course of neurogenesis. Experimental tests of the sufficiency of spindle/cleavage plane orientation in mammalian cell fate determination have yielded conflicting results. On the other hand, the necessity of spindle/cleavage plane orientation in mammalian cell fate determination has not yet been addressed. Here we examined the necessity of spindle/cleavage plane orientation during cortical neurogenesis in mice with loss-of-function of the RGS3-KIF20A interaction axis. We present evidence that while inactivation of RGS3 or KIF20A was linked to a shift in neural progenitor cells from proliferative to differentiative divisions in the developing cortex, these genetic mutations did not lead to anticipated alteration in the orientation of spindle/cleavage plane. Our results indicate that the RGS3-KIF20A axis regulates the balance between proliferation and differentiation in the mammalian cortex employing a mechanism independent of spindle/cleavage plane orientation. These data also caution against using spindle/cleavage plane orientation as the synonym for cell fate determination.