Centro Andaluz de Biología del Desarrollo (CSIC/UPO/JA), 41013, Sevilla, Spain.
Institute of Biological and Chemical Systems, Biological Information Processing (IBCS-BIP), Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
Nat Commun. 2023 May 16;14(1):2804. doi: 10.1038/s41467-023-38482-w.
The assembly of the embryo's primary axis is a fundamental landmark for the establishment of the vertebrate body plan. Although the morphogenetic movements directing cell convergence towards the midline have been described extensively, little is known on how gastrulating cells interpret mechanical cues. Yap proteins are well-known transcriptional mechanotransducers, yet their role in gastrulation remains elusive. Here we show that the double knockout of yap and its paralog yap1b in medaka results in an axis assembly failure, due to reduced displacement and migratory persistence in mutant cells. Accordingly, we identified genes involved in cytoskeletal organization and cell-ECM adhesion as potentially direct Yap targets. Dynamic analysis of live sensors and downstream targets reveal that Yap is acting in migratory cells, promoting cortical actin and focal adhesions recruitment. Our results indicate that Yap coordinates a mechanoregulatory program to sustain intracellular tension and maintain the directed cell migration for embryo axis development.
胚胎初级轴的组装是建立脊椎动物体轴模式的一个基本标志。尽管指导细胞向中线收敛的形态发生运动已经被广泛描述,但对于原肠胚细胞如何解释机械线索知之甚少。 Yap 蛋白是众所周知的转录机械转导因子,但它们在原肠胚形成中的作用仍不清楚。在这里,我们表明,在斑马鱼中敲除 yap 及其同源物 yap1b,由于突变细胞中位移减少和迁移持久性降低,导致轴组装失败。因此,我们鉴定了参与细胞骨架组织和细胞-ECM 黏附的基因,这些基因可能是 yap 的直接靶标。活传感器和下游靶标的动态分析表明,yap 在迁移细胞中起作用,促进皮质肌动蛋白和黏着斑的募集。我们的结果表明,yap 协调了一个机械调节程序,以维持细胞内张力,并维持胚胎轴发育的定向细胞迁移。