Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
J Cell Biol. 2012 Sep 3;198(5):941-52. doi: 10.1083/jcb.201203012.
Embryo morphogenesis is driven by dynamic cell behaviors, including migration, that are coordinated with fate specification and differentiation, but how such coordination is achieved remains poorly understood. During zebrafish gastrulation, endodermal cells sequentially exhibit first random, nonpersistent migration followed by oriented, persistent migration and finally collective migration. Using a novel transgenic line that labels the endodermal actin cytoskeleton, we found that these stage-dependent changes in migratory behavior correlated with changes in actin dynamics. The dynamic actin and random motility exhibited during early gastrulation were dependent on both Nodal and Rac1 signaling. We further identified the Rac-specific guanine nucleotide exchange factor Prex1 as a Nodal target and showed that it mediated Nodal-dependent random motility. Reducing Rac1 activity in endodermal cells caused them to bypass the random migration phase and aberrantly contribute to mesodermal tissues. Together, our results reveal a novel role for Nodal signaling in regulating actin dynamics and migration behavior, which are crucial for endodermal morphogenesis and cell fate decisions.
胚胎形态发生是由动态的细胞行为驱动的，包括迁移，这些行为与命运特化和分化相协调，但这种协调是如何实现的仍知之甚少。在斑马鱼原肠胚形成过程中，内胚层细胞依次经历最初的随机、非持续迁移，然后是定向、持续迁移，最后是集体迁移。使用一种新的转基因系标记内胚层肌动蛋白细胞骨架，我们发现迁移行为的这些阶段依赖性变化与肌动蛋白动力学的变化相关。早期原肠胚形成过程中表现出的动态肌动蛋白和随机运动依赖于 Nodal 和 Rac1 信号。我们进一步鉴定了 Rac 特异性鸟嘌呤核苷酸交换因子 Prex1 作为 Nodal 的靶标，并表明它介导了 Nodal 依赖性的随机运动。降低内胚层细胞中的 Rac1 活性会使它们跳过随机迁移阶段，并异常地参与中胚层组织的形成。总之，我们的研究结果揭示了 Nodal 信号在调节肌动蛋白动力学和迁移行为方面的新作用，这对内胚层形态发生和细胞命运决定至关重要。
