Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes.
Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes.
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DOI：
10.1083/jcb.201604015
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发表时间：
2016-11-21
期刊：
影响因子：
--
通讯作者：
Jenna S
中科院分区：
文献类型：
--
作者：
Martin E;Ouellette MH;Jenna S
GTPases Rac1 和 RhoA 之间的拮抗作用控制着胚胎发育过程中不同的形态发生过程。马丁等人。使用定量成像分析证明，RhoA 和 Rac1 样途径之间的细胞自主拮抗作用定义了秀丽隐杆线虫表皮形态发生过程中细胞间的异质性。 GTPase Rac1 和 RhoA 之间的拮抗作用控制体外等基因细胞群中的细胞间异质性和体内上皮形态发生。然而，它在表皮形态发生过程中细胞间异质性的调节中的作用从未被解决。我们使用定量细胞成像方法在单细胞水平上表征秀丽隐杆线虫胚胎早期伸长过程中的表皮形态发生。这项研究表明，涉及 Rac/Cdc42 鸟嘌呤交换因子 β-PIX/PIX-1 和效应器 PAK1/PAK-1 的 Rac1 样通路，以及涉及 ROCK/LET-502 的 RhoA 样通路，控制不同皮下细胞亚群中顶端连接的重塑和基底外侧突起的形成。在这些情况下，突起采用片状伪足或变形虫形态。我们认为，片层的形成可能会减少形态发生过程中细胞与细胞连接处的张力形成。这些途径之间的细胞自主拮抗作用使细胞能够在 Rac1 和 RhoA 样形态发生程序之间切换。这项研究首次发现了表皮形态发生过程中由 Rac1/RhoA 拮抗作用控制的细胞间异质性。
Antagonism between the GTPases Rac1 and RhoA controls different morphogenetic processes during embryonic development. Martin et al. use quantitative imaging analyses to demonstrate that cell-autonomous antagonism between the RhoA- and Rac1-like pathways defines cell-to-cell heterogeneity during epidermal morphogenesis in Caenorhabditis elegans. The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo. Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells. In these contexts, protrusions adopt lamellipodia or an amoeboid morphology. We propose that lamella formation may reduce tension building at cell–cell junctions during morphogenesis. Cell-autonomous antagonism between these pathways enables cells to switch between Rac1- and RhoA-like morphogenetic programs. This study identifies the first case of cell-to-cell heterogeneity controlled by Rac1/RhoA antagonism during epidermal morphogenesis.
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