Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Department of Genetics and Developmental Biology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
Dev Cell. 2020 Jun 8;53(5):589-602.e6. doi: 10.1016/j.devcel.2020.04.016. Epub 2020 May 20.
Despite much progress toward understanding how epithelial morphogenesis is shaped by intra-epithelial processes including contractility, polarity, and adhesion, much less is known regarding how such cellular processes are coordinated by extra-epithelial signaling. During embryogenesis, the coelomic epithelia on the two sides of the chick embryo undergo symmetrical lengthening and thinning, converging medially to generate and position the dorsal mesentery (DM) in the embryonic midline. We find that Hedgehog signaling, acting through downstream effectors Sec5 (ExoC2), an exocyst complex component, and RhoU (Wrch-1), a small GTPase, regulates coelomic epithelium morphogenesis to guide DM midline positioning. These effects are accompanied by changes in epithelial cell-cell alignment and N-cadherin and laminin distribution, suggesting Hedgehog regulation of cell organization within the coelomic epithelium. These results indicate a role for Hedgehog signaling in regulating epithelial morphology and provide an example of how transcellular signaling can modulate specific cellular processes to shape tissue morphogenesis.
尽管人们在理解上皮形态发生如何受到上皮内过程(包括收缩性、极性和粘附性)的影响方面取得了很大进展,但对于上皮外信号如何协调这些细胞过程知之甚少。在胚胎发生过程中,鸡胚两侧的体腔上皮经历对称的伸长和变薄,向中线汇聚以生成并定位背系膜(DM)在胚胎的中线上。我们发现 Hedgehog 信号通过下游效应物 Sec5(ExoC2)、外泌体复合物成分和 RhoU(Wrch-1)、小 GTPase 发挥作用,调节体腔上皮形态发生以指导 DM 中线定位。这些效应伴随着上皮细胞-细胞排列和 N-钙粘蛋白和层粘连蛋白分布的变化,表明 Hedgehog 调节体腔上皮内的细胞组织。这些结果表明 Hedgehog 信号在调节上皮形态方面的作用,并提供了一个例子,说明跨细胞信号如何调节特定的细胞过程来塑造组织形态发生。