PDF(Pubmed)
Abstract：
During epithelial morphogenesis, the apical junctions connecting cells must remodel as cells change shape and make new connections with their neighbors. In the C. elegans embryo, new apical junctions form when epidermal cells migrate and seal with one another to encase the embryo in skin (\'ventral enclosure\'), and junctions remodel when epidermal cells change shape to squeeze the embryo into a worm shape (\'elongation\'). The junctional cadherin-catenin complex (CCC), which links epithelial cells to each other and to cortical actomyosin, is essential for C. elegans epidermal morphogenesis. RNAi genetic enhancement screens have identified several genes encoding proteins that interact with the CCC to promote epidermal morphogenesis, including the scaffolding protein Afadin (AFD-1), whose depletion alone results in only minor morphogenesis defects. Here, by creating a null mutation in afd-1, we show that afd-1 provides a significant contribution to ventral enclosure and elongation on its own. Unexpectedly, we find that afd-1 mutant phenotypes are strongly modified by diet, revealing a previously unappreciated parental nutritional input to morphogenesis. We identify functional interactions between AFD-1 and the CCC by demonstrating that E-cadherin is required for the polarized distribution of AFD-1 to cell contact sites in early embryos. Finally, we show that afd-1 promotes the enrichment of polarity regulator, and CCC-interacting protein, PAC-1/ARHGAP21 to cell contact sites, and we identify genetic interactions suggesting that afd-1 and pac-1 regulate epidermal morphogenesis at least in part through parallel mechanisms. Our findings reveal that C. elegans AFD-1 makes a significant contribution to epidermal morphogenesis and functionally interfaces with core and associated CCC proteins.
摘要：
在上皮形态发生期间，当细胞改变形状并与邻居建立新的连接时，连接细胞的顶端连接必须重新建模。在秀丽隐杆线虫胚胎中，当表皮细胞迁移并相互密封以将胚胎包裹在皮肤中时，会形成新的顶端连接（“腹侧封闭”），当表皮细胞改变形状以将胚胎挤压成蠕虫形状（\'伸长\'）时，连接会重塑。连接钙粘蛋白-连环蛋白复合体(CCC)，将上皮细胞彼此连接并与皮质肌动球蛋白连接，是秀丽隐杆线虫表皮形态发生所必需的.RNAi基因增强筛选已经鉴定了几种编码与CCC相互作用以促进表皮形态发生的蛋白质的基因。包括支架蛋白Afadin（AFD-1），其耗尽仅导致轻微的形态发生缺陷。这里,通过在afd-1中创建无效突变，我们表明afd-1本身对腹侧封闭和延伸有显著贡献。出乎意料的是,我们发现afd-1突变表型被饮食强烈修饰，揭示了以前未被重视的父母对形态发生的营养投入。我们通过证明E-cadherin是AFD-1极化分布到早期胚胎中细胞接触位点所必需的，从而确定了AFD-1和CCC之间的功能相互作用。最后,我们表明，AFD-1促进极性调节剂的富集，和CCC相互作用蛋白，PAC-1/ARHGAP21连接到细胞接触点，我们确定了遗传相互作用，表明afd-1和pac-1至少部分通过平行机制调节表皮形态发生。我们的发现表明，秀丽隐杆线虫AFD-1对表皮形态发生以及与核心和相关CCC蛋白的功能接口做出了重大贡献。
