Institut de Biologia Molecular de Barcelona, CSIC, Parc Científic de Barcelona, Baldiri Reixac, 10-12, 08028 Barcelona, Spain.
J Cell Sci. 2011 Jan 15;124(Pt 2):240-51. doi: 10.1242/jcs.073601. Epub 2010 Dec 15.
Many epithelial tissues undergo extensive remodelling during morphogenesis. How their epithelial features, such as apicobasal polarity or adhesion, are maintained and remodelled and how adhesion and polarity proteins contribute to morphogenesis are two important questions in development. Here, we approach these issues by investigating the role of the apical determinant protein Crumbs (Crb) during the morphogenesis of the embryonic Drosophila tracheal system. Crb accumulates differentially throughout tracheal development and is required for different tracheal events. The earliest requirement for Crb is for tracheal invagination, which is preceded by an enhanced accumulation of Crb in the invagination domain. There, Crb, acting in parallel with the epidermal growth factor receptor (Egfr) pathway, is required for tracheal cell apical constriction and for organising an actomyosin complex, which we propose is mediated by Crb recruitment of moesin (Moe). The ability of a Crb isoform unable to rescue polarity in crb mutants to otherwise rescue their invagination phenotype, and the converse inability of a FERM-binding domain mutant Crb to rescue faulty invagination, support our hypothesis that it is the absence of Crb-dependent Moe enrichment, and not the polarity defect, that mainly underlies the crb invagination phenotype. This hypothesis is supported by the phenotype of lethal giant larvae (lgl); crb double mutants. These results unveil a link between Crb and the organisation of the actin cytoskeleton during morphogenesis.
许多上皮组织在形态发生过程中经历广泛的重塑。上皮特征（如顶端-基底极性或黏附）如何维持和重塑，以及黏附蛋白和极性蛋白如何促进形态发生，是发育中的两个重要问题。在这里，我们通过研究顶端决定蛋白 Crb 在胚胎果蝇气管系统形态发生中的作用来解决这些问题。Crb 在气管发育过程中差异积累，并需要参与不同的气管事件。Crb 的最早需求是气管内陷，在此之前，Crb 在内陷区域的积累增强。在那里，Crb 与表皮生长因子受体（Egfr）途径平行作用，需要气管细胞顶端收缩，并组织肌动球蛋白复合物，我们提出这是由 Crb 招募 moesin（Moe）介导的。一种不能拯救 crb 突变体极性的 Crb 异构体能够拯救其内陷表型，而不能拯救错误内陷的 FERM 结合域突变 Crb，这支持了我们的假设，即主要是 Crb 依赖性 Moe 富集的缺失，而不是极性缺陷，是 crb 内陷表型的基础。这一假设得到了致死性巨幼虫（lgl）；crb 双突变体的表型的支持。这些结果揭示了 Crb 与形态发生过程中肌动蛋白细胞骨架组织之间的联系。
