Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, New York 10065, USA.
Semin Cell Dev Biol. 2022 Sep;129:63-74. doi: 10.1016/j.semcdb.2022.05.005. Epub 2022 May 13.
Cellular protrusions generated by the actin cytoskeleton are central to the process of building the body of the embryo. Problems with cellular protrusions underlie human diseases and syndromes, including implantation defects and pregnancy loss, congenital birth defects, and cancer. Cells use protrusive activity together with actin-myosin contractility to create an ordered body shape of the embryo. Here, I review how actin-rich protrusions are used by two major morphological cell types, epithelial and mesenchymal cells, during collective cell migration to sculpt the mouse embryo body. Pre-gastrulation epithelial collective migration of the anterior visceral endoderm is essential for establishing the anterior-posterior body axis. Gastrulation mesenchymal collective migration of the mesoderm wings is crucial for body elongation, and somite and heart formation. Analysis of mouse mutants with disrupted cellular protrusions revealed the key role of protrusions in embryonic morphogenesis and embryo survival. Recent technical approaches have allowed examination of the mechanisms that control cell and tissue movements in vivo in the complex 3D microenvironment of living mouse embryos. Advancing our understanding of protrusion-driven morphogenesis should provide novel insights into human developmental disorders and cancer metastasis.
细胞突起是由肌动蛋白细胞骨架产生的,对于构建胚胎体的过程至关重要。细胞突起的问题是人类疾病和综合征的基础,包括着床缺陷和妊娠丢失、先天性出生缺陷和癌症。细胞使用突起活动和肌动球蛋白收缩力来创建胚胎的有序体型。在这里,我回顾了富含肌动蛋白的突起如何被两种主要的形态细胞类型——上皮细胞和间充质细胞——在集体细胞迁移过程中使用,以塑造小鼠胚胎体。前原肠胚期上皮细胞的集体迁移对于建立前后体轴是必不可少的。原肠胚期中胚层的集体迁移对于胚胎的伸长、体节和心脏的形成至关重要。对细胞突起中断的小鼠突变体的分析揭示了突起在胚胎形态发生和胚胎存活中的关键作用。最近的技术方法允许在活体小鼠胚胎复杂的 3D 微环境中体内检查控制细胞和组织运动的机制。深入了解突起驱动的形态发生应该为人类发育障碍和癌症转移提供新的见解。