Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching
Axis specification and morphogenesis in the mouse embryo require Nap1, a regulator of WAVE-mediated actin branching
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DOI：
10.1242/dev.02473
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发表时间：
2006-08-15
期刊：
影响因子：
4.6
通讯作者：
Anderson, Kathryn V.
中科院分区：
文献类型：
--
作者：
Rakeman, Andrew S.;Anderson, Kathryn V.
动态的细胞运动和重排对于哺乳动物身体计划的产生是必不可少的，尽管对协调细胞运动和细胞命运的基因知之甚少。WAVE复合物是肌动蛋白细胞骨架的调节剂，其将细胞外信号耦合到极化细胞运动。在这里，我们表明，小鼠胚胎缺乏Nap 1，一个监管组成部分的波复杂，逮捕在妊娠中期，并有缺陷的形态发生的所有三个胚胎胚层。在Nap 1突变体中检测不到WAVE蛋白，WAVE复合物的其他组分不能定位于Nap 1突变体细胞的表面;因此Nap 1的缺失似乎使WAVE复合物在体内消失。Nap 1突变体表现出特定的形态发生缺陷：它们不能关闭神经管，不能形成单个心管（心裂），并表现出内胚层和中胚层的延迟迁移。在没有Nap 1/WAVE活性的情况下，其他形态发生过程似乎正常进行：脊索、心脏层和原肠胚形成时的上皮-间充质转化（EMT）似乎正常。在大约四分之一的Nap 1突变体中看到的一个引人注目的表型是前后体轴的重复。轴复制的出现是因为Nap 1是前内脏内胚层（AVE）细胞（早期胚外组织者组织）正常极化和迁移所必需的。因此，Nap 1突变体表型de.新的Nap 1/WAVE介导的肌动蛋白调节的组织组织和哺乳动物胚胎的身体计划的建立中的关键作用。
Dynamic cell movements and rearrangements are essential for the generation of the mammalian body plan, although relatively little is known about the genes that coordinate cell movement and cell fate. WAVE complexes are regulators of the actin cytoskeleton that couple extracellular signals to polarized cell movement. Here, we show that mouse embryos that lack Nap1, a regulatory component of the WAVE complex, arrest at midgestation and have defects in morphogenesis of all three embryonic germ layers. WAVE protein is not detectable in Nap1 mutants, and other components of the WAVE complex fail to localize to the surface of Nap1 mutant cells; thus loss of Nap1 appears to inactivate the WAVE complex in vivo. Nap1 mutants show specific morphogenetic defects: they fail to close the neural tube, fail to form a single heart tube (cardia bifida), and show delayed migration of endoderm and mesoderm. Other morphogenetic processes appear to proceed normally in the absence of Nap1/WAVE activity: the notochord, the layers of the heart, and the epithelial-to-mesenchymal transition (EMT) at gastrulation appear normal. A striking phenotype seen in approximately one quarter of Nap1 mutants is the duplication of the anteroposterior body axis. The axis duplications arise because Nap1 is required for the normal polarization and migration of cells of the Anterior Visceral Endoderm (AVE), an early extraembryonic organizer tissue. Thus, the Nap1 mutant phenotypes de. ne the crucial roles of Nap1/WAVE-mediated actin regulation in tissue organization and establishment of the body plan of the mammalian embryo.