Dual Roles of Notch in Regulation of Apically Restricted Mitosis and Apicobasal Polarity of Neuroepithelial Cells
Dual Roles of Notch in Regulation of Apically Restricted Mitosis and Apicobasal Polarity of Neuroepithelial Cells
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DOI：
10.1016/j.neuron.2010.12.026
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发表时间：
2011-01-27
期刊：
影响因子：
16.2
通讯作者：
Okamoto, Hitoshi
中科院分区：
文献类型：
--
作者：
Ohata, Shinya;Aoki, Ryo;Okamoto, Hitoshi
神经上皮干细胞的有丝分裂是如何局限于顶室区的仍不清楚。在斑马鱼中，嵌合眼（rw 306）（莫伊/epb 41 I5（rw 306））突变破坏了假定的衔接蛋白莫伊和顶基极性调节Crumbs（Crb）之间的相互作用，并损害神经上皮顶基极性的维持。虽然Crb直接与Notch相互作用并抑制其活性，但莫伊逆转了这种抑制作用。在莫伊（rw 306）后脑中，Notch活性显著降低，并且远离顶端区域的基底增殖的细胞数量增加。令人惊讶的是，Notch在莫伊（rw 306）突变体中的激活不仅挽救了基底局部增殖，而且挽救了异常的神经上皮顶基底极性。我们提出的证据表明，Crb.莫伊复合物和Notch在正反馈回路中发挥关键作用，以维持神经上皮细胞中Notch活性的顶基极性和顶基-高基-低梯度，这两者对于其顶基限制有丝分裂是必不可少的。
How the mitosis of neuroepithelial stem cells is restricted to the apical ventricular area remains unclear. In zebrafish, the mosaic eyes(rw306) (moe/epb41I5(rw306)) mutation disrupts the interaction between the putative adaptor protein Moe and the apicobasal polarity regulator Crumbs (Crb), and impairs the maintenance of neuroepithelial apicobasal polarity. While Crb interacts directly with Notch and inhibits its activity, Moe reverses this inhibition. In the moe(rw306) hindbrain, Notch activity is significantly reduced, and the number of cells that proliferate basally away from the apical area is increased. Surprisingly, activation of Notch in the moe(rw306) mutant rescues not only the basally localized proliferation but also the aberrant neuroepithelial apicobasal polarity. We present evidence that the Crb.Moe complex and Notch play key roles in a positive feedback loop to maintain the apicobasal polarity and the apical-high basal-low gradient of Notch activity in neuroepithelial cells, both of which are essential for their apically restricted mitosis.