Neural Development Group, Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee, UK.
EMBO Rep. 2012 May 1;13(5):448-54. doi: 10.1038/embor.2012.42.
Inheritance of apical membrane is proposed to maintain vertebrate neural stem cell proliferation. However, evidence for this is contradictory. Using direct clonal analysis and live imaging in chick neural tube, we show that divisions that separate apical and basal components generate an apical daughter, which becomes a neuron, and a basal daughter, which rapidly re-establishes apico-basal polarity and divides again. Using a recently described real-time reporter of Notch activity, we confirm progenitor status and demonstrate that division orientation can influence Notch signalling. In addition, we reveal loss of apical complex proteins on neuronal differentiation onset, suggesting that removal of this inherited complex is part of the neuronal differentiation mechanism. These findings reconcile contradictory data, link asymmetric division to Notch signalling dynamics and identify apical complex loss as a new step towards neuronal differentiation.
顶端膜的遗传被认为是维持脊椎动物神经干细胞增殖的原因。然而,这方面的证据存在矛盾。通过鸡神经管中的直接克隆分析和实时成像,我们表明,分离顶端和基底部分的分裂产生了一个顶端子细胞,它会成为一个神经元,而一个基底子细胞会迅速重新建立顶端-基底极性并再次分裂。利用最近描述的 Notch 活性实时报告器,我们证实了祖细胞的状态,并证明了分裂方向可以影响 Notch 信号。此外,我们还揭示了神经元分化起始时顶端复合物蛋白的丢失,这表明这种遗传复合物的去除是神经元分化机制的一部分。这些发现调和了矛盾的数据,将不对称分裂与 Notch 信号动力学联系起来,并确定顶端复合物的丢失是神经元分化的一个新步骤。