Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors
Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors
复制标题
DOI：
10.1073/pnas.0705713105
复制
发表时间：
2008-01-08
影响因子：
11.1
通讯作者：
Hunter, Tony
中科院分区：
文献类型：
--
作者：
Ghosh, Sourav;Marquard, Till;Hunter, Tony
在中枢神经系统发育的神经发生阶段，增殖的前体细胞位于神经上皮细胞的内侧。增殖中的神经前体细胞顶膜上的黏附连接允许细胞间黏附和中层复层。相反，分化的神经元前体分层并横向迁移，建立板层。顶端粘连连接也在神经前体细胞中建立了顶端-基底端的极性，这反过来被认为导致了神经源性分裂过程中细胞命运决定因素的不对称遗传。调节神经前体细胞中黏附连接的组装和不对称定位的信号通路和细胞机制仍然难以捉摸。在这里，我们发现非典型的PKC Zeta/lambda(aPKC Zeta/lambda)在发育中的鸡神经管中定位于增殖的神经干细胞的顶膜，而不是有丝分裂后的神经元前体。这种精确的亚细胞划分为PI3K、RAC/CDC42信号依赖通路中黏附连接的顶端组装提供了一个有指导意义的信号。顶端aPKC Zeta协调神经干细胞的增殖和神经管内细胞类型的整体分层。
In the neurogenic phase of CNS development, the proliferating progenitors are found medially within the neuroepithelium. The adherens junctions on the apical membrane of proliferating neural progenitors allow for cell-cell adhesion and medial stratification. In contrast, differentiating neuronal precursors delaminate and migrate laterally, establishing the laminar layers. Apical adherens junctions also establish the apical-basal polarity in neural progenitors, which in turn is postulated to lead to asymmetric inheritance of cell fate determinants during neurogenic divisions. The signaling pathways and cellular mechanisms that regulate the assembly and asymmetric localization of adherens junctions in neural progenitors remain elusive. Here we show that atypical PKC zeta/lambda(aPKC zeta/lambda ) localizes at the apical membrane of proliferating neural stem cells, but not postmitotic neuronal precursors, in the developing chicken neural tube. This precise subcellular compartmentalization of the kinase activity provides an instructive signal for apical assembly of adherens junctions in a PI3K, Rac/Cdc42 signaling-dependent pathway. Apical aPKC zeta coordinates neural stem cell proliferation and the overall stratification of cell types within the neural tube.