Cui Shuang, Otten Cécile, Rohr Stefan, Abdelilah-Seyfried Salim, Link Brian A
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Mol Cell Neurosci. 2007 Mar;34(3):431-44. doi: 10.1016/j.mcn.2006.11.016. Epub 2007 Jan 12.
Retinal lamination is known to depend on cell polarity and localized signaling. In vertebrates, atypical protein kinase C proteins, aPKClambda/iota and aPKCzeta, are essential for apical-basal cell polarity. However, it is not known to what extent functional redundancy has precluded a comprehensive functional characterization of aPKC signaling during vertebrate retinogenesis. Here, we show that aPKCs lambda and zeta are functionally redundant for multiple aspects of retinogenesis including mitotic division location and orientation, cell-type positioning, and retinal pigment epithelial (RPE) and photoreceptor cell morphogenesis. Genetic mosaic analyses demonstrate a cell-autonomous requirement of aPKCs for RPE and photoreceptor development, and a cell-non-cell-autonomous function that is intrinsic to the neural retina for cell-type positioning. Our observations uncover a previously unappreciated involvement of aPKCzeta during zebrafish retinogenesis and suggest that aPKC signaling primes the retinal environment for appropriate cell migration of post-mitotic progenitor cells but is not essential for correct cell-type specification.
已知视网膜分层依赖于细胞极性和局部信号传导。在脊椎动物中，非典型蛋白激酶C蛋白，即aPKClambda/iota和aPKCzeta，对于顶-基细胞极性至关重要。然而，在脊椎动物视网膜发育过程中，功能冗余在多大程度上阻碍了对aPKC信号传导的全面功能表征尚不清楚。在这里，我们表明aPKC lambda和zeta在视网膜发育的多个方面功能冗余，包括有丝分裂分裂位置和方向、细胞类型定位以及视网膜色素上皮（RPE）和光感受器细胞形态发生。基因镶嵌分析表明，aPKC对RPE和光感受器发育具有细胞自主需求，并且对细胞类型定位具有神经视网膜固有的非细胞自主功能。我们的观察结果揭示了aPKCzeta在斑马鱼视网膜发育过程中以前未被认识到的参与，并表明aPKC信号传导为有丝分裂后祖细胞的适当细胞迁移准备视网膜环境，但对于正确的细胞类型指定不是必需的。
