Zou Jian, Wen Yi, Yang Xiaojun, Wei Xiangyun
Department of Ophthalmology, University of Pittsburgh School of Medicine, 3501 Fifth Avenue, Pittsburgh, PA 15213, United States.
Int J Dev Neurosci. 2013 Dec;31(8):770-82. doi: 10.1016/j.ijdevneu.2013.09.005. Epub 2013 Sep 24.
A vast number of apicobasal polarity proteins play essential roles in the polarization and morphogenesis of the neuroepithelia. Crumbs (Crb) type I transmembrane cell-cell adhesion proteins are among these proteins. Five crb genes have been identified in zebrafish. However, their expressional and functional differences during early neural development remain to be fully elucidated. Here, we study the spatial-temporal expression patterns and functions of Crb1, Crb2a, and Crb2b in the central nervous system (CNS) during the neurulation period. We show that: 1, the optic vesicle and undifferentiated retinal neuroepithelium only express Crb2a; 2, Crb1 and Crb2a expressions overlap extensively in the undifferentiated neural tube epithelium; 3, Crb2b expression is the weakest of the three and is restricted to the ventral-most regions of the anterior CNS; and 4, Nok and Crb proteins require each other for their apical localization in neuroepithelium. The commencements of Crb1, Crb2a, and Crb2b expressions follow a spatial-temporal spread from anterior to posterior and from ventral to dorsal and lag behind that of adherens junction components, such as ZO-1 and actin bundles. Genetic and morpholino suppression analyses suggest that in regions where these Crb expressions overlap, they are functionally redundant in maintaining apicobasal polarity of the undifferentiated neuroepithelium.
大量的顶-基极性蛋白在神经上皮的极化和形态发生中发挥着重要作用。Crb(crumbs)家族的I型跨膜细胞-细胞粘附蛋白就在这些蛋白之中。斑马鱼中已鉴定出五个crb基因。然而,它们在早期神经发育过程中的表达和功能差异仍有待充分阐明。在此,我们研究了神经胚形成期Crb1、Crb2a和Crb2b在中枢神经系统(CNS)中的时空表达模式和功能。我们发现:1,视泡和未分化的视网膜神经上皮仅表达Crb2a;2,Crb1和Crb2a在未分化的神经管上皮中广泛重叠表达;3,Crb2b的表达是三者中最弱的,且局限于前脑中枢神经系统最腹侧的区域;4,Nok和Crb蛋白在神经上皮中的顶端定位需要相互依赖。Crb1、Crb2a和Crb2b的表达起始呈现从前向后、从腹侧向背侧的时空扩散,且落后于紧密连接成分(如ZO-1和肌动蛋白束)。基因和吗啉代抑制分析表明,在这些Crb表达重叠的区域,它们在维持未分化神经上皮的顶-基极性方面功能冗余。