Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis

Neuroepithelial progenitors undergo LGN-dependent planar divisions to maintain self-renewability during mammalian neurogenesis
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DOI:
10.1038/ncb1673
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发表时间:
2008-01-01
影响因子:
21.3
通讯作者:
Matsuzaki, Fumio
Matsuzaki, Fumio
中科院分区:
生物学1区
文献类型:
--
作者:
Konno, Daijiro;Shioi, Go;Matsuzaki, Fumio

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在哺乳动物发育过程中,神经上皮细胞作为有丝分裂祖细胞发挥功能,其自我更新并产生神经元。虽然纺锤体取向对于这种极化细胞进行对称或不对称分裂是重要的(1,2),但其在哺乳动物神经发生中的作用仍不清楚。在这里,我们表明,纺锤体方向的控制是必不可少的,在维持人口的神经上皮细胞,但不确定的决定,无论是增殖或分化。敲除LGN(G蛋白调节剂)(3,4),使正常平面神经上皮分裂的方向随机化。由此产生的子细胞顶端膜的丢失经常将它们转化为异常定位的祖细胞,而不影响神经元的产生速率。此外,诱导垂直神经上皮分裂的Inscuteable(5)的过表达改变了子细胞的命运。我们的研究结果表明,平面有丝分裂确保自我更新的神经上皮祖细胞的一个女儿继承顶端和基底室在神经发生。
During mammalian development, neuroepithelial cells function as mitotic progenitors, which self-renew and generate neurons. Although spindle orientation is important for such polarized cells to undergo symmetric or asymmetric divisions(1,2), its role in mammalian neurogenesis remains unclear. Here we show that control of spindle orientation is essential in maintaining the population of neuroepithelial cells, but dispensable for the decision to either proliferate or differentiate. Knocking out LGN, (the G protein regulator)(3,4), randomized the orientation of normally planar neuroepithelial divisions. The resultant loss of the apical membrane from daughter cells frequently converted them into abnormally localized progenitors without affecting neuronal production rate. Furthermore, overexpression of Inscuteable(5) to induce vertical neuroepithelial divisions shifted the fate of daughter cells. Our results suggest that planar mitosis ensures the self-renewal of neuroepithelial progenitors by one daughter inheriting both apical and basal compartments during neurogenesis.