RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Neuron. 2011 Jan 27;69(2):215-30. doi: 10.1016/j.neuron.2010.12.026.
How the mitosis of neuroepithelial stem cells is restricted to the apical ventricular area remains unclear. In zebrafish, the mosaic eyes(rw306) (moe/epb41l5(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.
神经上皮干细胞的有丝分裂如何被限制在顶端脑室区域尚不清楚。在斑马鱼中，镶嵌眼（rw306）（moe/epb41l5（rw306））突变破坏了假定的衔接蛋白 Moe 和顶端基底极性调节剂 Crumbs（Crb）之间的相互作用，并损害了神经上皮顶端基底极性的维持。虽然 Crb 直接与 Notch 相互作用并抑制其活性，但 Moe 逆转了这种抑制。在 moe（rw306）后脑中，Notch 活性显著降低，从顶端区域基底增殖的细胞数量增加。令人惊讶的是，Notch 在 moe（rw306）突变体中的激活不仅挽救了基底定位的增殖，而且挽救了异常的神经上皮顶端基底极性。我们提供的证据表明，Crb⋅Moe 复合物和 Notch 在维持神经上皮细胞顶端基底极性和 Notch 活性的顶端高基底低梯度的正反馈回路中发挥关键作用，这两者对于它们顶端限制的有丝分裂都是必不可少的。
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