Shi Jianli, Zhao Ying, Galati Domenico, Winey Mark, Klymkowsky Michael W
Molecular, Cellular, & Developmental Biology, University of Colorado, Boulder, CO 80309-347, USA.
Molecular, Cellular, & Developmental Biology, University of Colorado, Boulder, CO 80309-347, USA.
Dev Biol. 2014 Nov 15;395(2):287-98. doi: 10.1016/j.ydbio.2014.09.008. Epub 2014 Sep 16.
Wnt signaling and ciliogenesis are core features of embryonic development in a range of metazoans. Chibby (Cby), a basal-body associated protein, regulates β-catenin-mediated Wnt signaling in the mouse but not Drosophila. Here we present an analysis of Cby's embryonic expression and morphant phenotypes in Xenopus laevis. Cby RNA is supplied maternally, negatively regulated by Snail2 but not Twist1, preferentially expressed in the neuroectoderm, and regulates β-catenin-mediated gene expression. Reducing Cby levels reduced the density of multiciliated cells, the number of basal bodies per multiciliated cell, and the numbers of neural tube primary cilia; it also led to abnormal development of the neural crest, central nervous system, and pronephros, all defects that were rescued by a Cby-GFP chimera. Reduction of Cby led to an increase in Wnt8a and decreases in Gli2, Gli3, and Shh RNA levels. Many, but not all, morphant phenotypes were significantly reversed by the Wnt inhibitor SFRP2. These observations extend our understanding of Cby's role in mediating the network of interactions between ciliogenesis, signaling systems and tissue patterning.
Wnt信号传导和纤毛发生是一系列后生动物胚胎发育的核心特征。Chibby（Cby）是一种与基体相关的蛋白质，它在小鼠中调节β-连环蛋白介导的Wnt信号传导，但在果蝇中则不然。在这里，我们展示了对非洲爪蟾中Cby的胚胎表达和形态缺陷型表型的分析。Cby RNA由母体提供，受Snail2而非Twist1的负调控，优先在神经外胚层中表达，并调节β-连环蛋白介导的基因表达。降低Cby水平会降低多纤毛细胞的密度、每个多纤毛细胞的基体数量以及神经管初级纤毛的数量；它还会导致神经嵴、中枢神经系统和前肾的异常发育，所有这些缺陷都可被Cby-GFP嵌合体挽救。Cby的减少导致Wnt8a增加，Gli2、Gli3和Shh RNA水平降低。许多（但不是全部）形态缺陷型表型被Wnt抑制剂SFRP2显著逆转。这些观察结果扩展了我们对Cby在介导纤毛发生、信号系统和组织模式形成之间相互作用网络中作用的理解。
