Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Development. 2022 May 15;149(10). doi: 10.1242/dev.200236. Epub 2022 May 16.
Apical constriction, or a reduction in size of the apical domain, underlies many morphogenetic events during development. Actomyosin complexes play an essential role in apical constriction; however, the detailed analysis of molecular mechanisms is still pending. Here, we show that Lim domain only protein 7 (Lmo7), a multidomain adaptor at apical junctions, promotes apical constriction in the Xenopus superficial ectoderm, whereas apical domain size increases in Lmo7-depleted cells. Lmo7 is primarily localized at apical junctions and promotes the formation of the dense circumferential actomyosin belt. Strikingly, Lmo7 binds non-muscle myosin II (NMII) and recruits it to apical junctions and the apical cortex. This NMII recruitment is essential for Lmo7-mediated apical constriction. Lmo7 knockdown decreases NMIIA localization at apical junctions and delays neural tube closure in Xenopus embryos. Our findings suggest that Lmo7 serves as a scaffold that regulates actomyosin contractility and apical domain size.
顶端缢缩,或顶端区域的尺寸减小,是发育过程中许多形态发生事件的基础。肌动球蛋白复合物在顶端缢缩中起着至关重要的作用;然而,分子机制的详细分析仍在进行中。在这里,我们表明,顶端连接的多功能衔接蛋白 Lim 域仅蛋白 7(Lmo7)促进了非洲爪蟾浅层外胚层的顶端缢缩,而 Lmo7 耗尽的细胞中顶端区域的大小增加。Lmo7 主要定位于顶端连接,并促进密集的圆周肌动球蛋白带的形成。引人注目的是,Lmo7 结合非肌肉肌球蛋白 II(NMII)并将其募集到顶端连接和顶端皮质。这种 NMII 的募集对于 Lmo7 介导的顶端缢缩是必不可少的。Lmo7 的敲低会减少 NMIIA 在顶端连接的定位,并延迟非洲爪蟾胚胎神经管的闭合。我们的研究结果表明,Lmo7 作为一种支架,调节肌动球蛋白的收缩性和顶端区域的大小。