PDF(Pubmed)
Abstract：
Mediolateral cell intercalation is a morphogenetic strategy used throughout animal development to reshape tissues. Dorsal intercalation in the Caenorhabditis elegans embryo involves the mediolateral intercalation of two rows of dorsal epidermal cells to create a single row that straddles the dorsal midline, and thus is a simple model to study cell intercalation. Polarized protrusive activity during dorsal intercalation requires the C. elegans Rac and RhoG orthologs CED-10 and MIG-2, but how these GTPases are regulated during intercalation has not been thoroughly investigated. In this study, we characterized the role of the Rac-specific guanine nucleotide exchange factor (GEF) TIAM-1 in regulating actin-based protrusive dynamics during dorsal intercalation. We found that TIAM-1 can promote formation of the main medial lamellipodial protrusion extended by intercalating cells through its canonical GEF function, whereas its N-terminal domains function to negatively regulate the generation of ectopic filiform protrusions around the periphery of intercalating cells. We also show that the guidance receptor UNC-5 inhibits these ectopic filiform protrusions in dorsal epidermal cells and that this effect is in part mediated via TIAM-1. These results expand the network of proteins that regulate basolateral protrusive activity during directed rearrangement of epithelial cells in animal embryos.
摘要：
中外侧细胞嵌入是一种在整个动物发育过程中用于重塑组织的形态发生策略。秀丽隐杆线虫胚胎的背侧插入涉及两排背侧表皮细胞的中外侧插入，以创建横跨背侧中线的单排，因此是研究细胞嵌入的简单模型。背侧嵌入过程中的极化突出活动需要秀丽隐杆线虫Rac和RhoG直向同源物CED-10和MIG-2，但是在嵌入过程中如何调节这些GTP酶尚未得到彻底研究。在这项研究中,我们描述了Rac特异性鸟嘌呤核苷酸交换因子(GEF)的作用，TIAM-1，在背侧嵌入过程中调节基于肌动蛋白的突出动力学。我们发现TIAM-1可以通过其规范的GEF功能促进由嵌入细胞延伸的主要内侧层状突起的形成，而其N端结构域的作用是负调节嵌入细胞周围异位丝状突起的产生。我们还表明，引导受体UNC-5抑制背侧表皮细胞中的这些异位丝状突起，并且这种作用部分是通过TIAM-1介导的。这些结果扩展了在动物胚胎中上皮细胞定向重排过程中调节基底外侧突出活动的蛋白质网络。
