Ghosh Sourav, Marquardt Till, Thaler Joshua P, Carter Nigel, Andrews Shane E, Pfaff Samuel L, Hunter Tony
Molecular and Cell Biology Laboratory and Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):335-40. doi: 10.1073/pnas.0705713105. Epub 2007 Dec 27.
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 PKCzeta/lambda (aPKCzeta/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 aPKCzeta coordinates neural stem cell proliferation and the overall stratification of cell types within the neural tube.
在中枢神经系统发育的神经源性阶段,增殖的祖细胞位于神经上皮内侧。增殖的神经祖细胞顶端膜上的黏着连接允许细胞间黏附并形成内侧分层。相反,正在分化的神经元前体细胞脱层并向外侧迁移,形成层状结构。顶端黏着连接还在神经祖细胞中建立顶端-基底极性,进而推测其在神经源性分裂过程中导致细胞命运决定因子的不对称遗传。调节神经祖细胞中黏着连接组装和不对称定位的信号通路和细胞机制仍不清楚。在这里,我们表明,在发育中的鸡神经管中,非典型蛋白激酶Cζ/λ(aPKCζ/λ)定位于增殖神经干细胞的顶端膜,而不定位于有丝分裂后的神经元前体细胞。激酶活性的这种精确亚细胞区室化在PI3K、Rac/Cdc42信号依赖途径中为黏着连接的顶端组装提供了一个指导性信号。顶端aPKCζ协调神经干细胞增殖和神经管内细胞类型的整体分层。