A ratchet-like apical constriction drives cell ingression during the mouse gastrulation EMT.
A ratchet-like apical constriction drives cell ingression during the mouse gastrulation EMT.
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DOI：
10.7554/elife.84019
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发表时间：
2023-05-10
期刊：
影响因子：
7.7
通讯作者：
Hadjantonakis AK
中科院分区：
文献类型：
--
作者：
Francou A;Anderson KV;Hadjantonakis AK
上皮-间充质转化（EMT）是上皮细胞获得间充质表型和迁移能力的基本过程。EMT是原肠胚形成的标志，这是一个进化上保守的发育过程。在哺乳动物中，外胚层细胞在原始条纹处进入形成中胚层。细胞进入和退出外胚层和相关的EMT是动态调节的，涉及细胞行为的典型序列。原肠胚的三维延时成像结合细胞和组织尺度数据分析显示，外胚层细胞在原始条纹处异步侵入。进入细胞通过顶端连接的异步收缩，以脉冲棘轮状的方式收缩其顶端表面。对顶端蛋白分布的定量分析揭示了肌动球蛋白网络和Crumbs2复合物成员的各向异性和互惠富集，这些成员是细胞连接异步收缩的潜在调节因子。功能缺失分析表明，Crumbs2在肌凝蛋白II的定位和顶端连接的活性中是必需的，并且是肌动球蛋白各向异性的候选调节因子。
Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells acquire mesenchymal phenotypes and the ability to migrate. EMT is the hallmark of gastrulation, an evolutionarily conserved developmental process. In mammals, epiblast cells ingress at the primitive streak to form mesoderm. Cells ingress and exit the epiblast epithelial layer and the associated EMT is dynamically regulated and involves a stereotypical sequence of cell behaviors. 3D time-lapse imaging of gastrulating mouse embryos combined with cell and tissue scale data analyses revealed the asynchronous ingression of epiblast cells at the primitive streak. Ingressing cells constrict their apical surfaces in a pulsed ratchet-like fashion through asynchronous shrinkage of apical junctions. A quantitative analysis of the distribution of apical proteins revealed the anisotropic and reciprocal enrichment of members of the actomyosin network and Crumbs2 complexes, potential regulators of asynchronous shrinkage of cell junctions. Loss of function analyses demonstrated a requirement for Crumbs2 in myosin II localization and activity at apical junctions, and as a candidate regulator of actomyosin anisotropy.