Martin-Bermudo M D, Brown N H
Wellcome Trust/Cancer Research Campaign Institute of Cancer and Developmental Biology, and Department of Anatomy, University of Cambridge, Cambridge CB2 1QR, UK.
Genes Dev. 1999 Mar 15;13(6):729-39. doi: 10.1101/gad.13.6.729.
Integrin cell surface receptors are ideally suited to coordinate cellular differentiation and tissue assembly during embryogenesis, as they can mediate both signaling and adhesion. We show that integrins regulate gene expression in the intact developing embryo by identifying two genes that require integrin function for their normal expression in Drosophila midgut endodermal cells. We determined the relative roles of integrin adhesion versus signaling in the regulation of these integrin target genes. We find that integrin-mediated adhesion is not required between the endodermal cells and the surrounding visceral mesoderm for integrin target gene expression. In addition, a chimeric protein that lacks integrin-adhesive function, but maintains the ability to signal, can substitute for the endogenous integrin and regulate integrin target genes. This chimera consists of an oligomeric extracellular domain fused to the integrin betaPS subunit cytoplasmic domain; a control monomeric extracellular domain fusion does not alter integrin target gene expression. Therefore, oligomerization of the 47-amino-acid betaPS intracellular domain is sufficient to initiate a signaling pathway that regulates gene expression in the developing embryo.
整合素细胞表面受体非常适合在胚胎发育过程中协调细胞分化和组织组装，因为它们既能介导信号传导又能介导黏附。我们通过鉴定两个在果蝇中肠内胚层细胞中正常表达需要整合素功能的基因，表明整合素在完整的发育胚胎中调节基因表达。我们确定了整合素黏附与信号传导在这些整合素靶基因调控中的相对作用。我们发现，内胚层细胞与周围内脏中胚层之间的整合素介导的黏附对于整合素靶基因表达并非必需。此外，一种缺乏整合素黏附功能但保持信号传导能力的嵌合蛋白可以替代内源性整合素并调节整合素靶基因。这种嵌合体由与整合素βPS亚基胞质结构域融合的寡聚细胞外结构域组成；对照单体细胞外结构域融合不会改变整合素靶基因表达。因此，47个氨基酸的βPS细胞内结构域的寡聚化足以启动一条调节发育胚胎中基因表达的信号通路。
