Defining the roles of endothelial integrins during mammary gland development, functional differentiation, and involution (SSA)

血管形成（血管生成）和重组在胚胎发育中起着至关重要的作用，对于维持健康的生理过程至关重要，例如伤口愈合和月经周期期间子宫壁的重建。随着年龄的增长，这些过程的效果越来越差，血管生成的错误调节导致了许多恶性、炎症、缺血、感染和免疫疾病。因此，增加我们对血管生成调节的理解将使我们能够操纵它来维持健康和修复疾病。我们的实验室对内皮纤维连接蛋白结合整合素的作用感兴趣，因为它们在血管生成血管中上调。我们和其他人最近的证据表明，这两种整合素在许多胚胎器官的血管形成中起着重要作用。利用条件性基因敲除小鼠模型，本项目将探索其内皮表达如何影响乳腺发育和功能分化。乳腺是少数几个在出生后经历上皮/基质生长和形态发生（妊娠期间）、分化和功能活动（哺乳期间）以及退化（断奶后）周期的器官之一。使用从相同小鼠模型的乳腺中分离的内皮细胞，该项目还将研究这两种整合素如何在体外协同调节内皮细胞行为。

Blood vessel formation (angiogenesis) and re-organisation play essential roles in embryonic development and are critical for maintaining healthy physiological processes such as wound healing and the restructuring of the uterine wall during the menstrual cycle. These process works less effectively as we age and mis-regulation of angiogenesis contributes to a multitude of malignant, inflammatory, ischaemic, infectious and immune disorder. Thus increasing our understanding of angiogenesis regulation will allow us to manipulate it to maintain health and repair disease throughout life. Our lab is interested in the role of the endothelial fibronectin binding integrins because of their up-regulation in angiogenic vasculature. Recent evidence from us, and others, indicates these two integrins play instrumental roles in the formation of the vasculature of a number of embryonic organs. Using conditional knockout mouse models, this project will explore how their endothelial expression influences mammary gland development and functional differentiation. The mammary gland is one of the few organs to undergo cycles of epithelial/stromal growth & morphogenesis (during pregnancy), differentiation & functional activity (during lactation), and involution (after weaning) in post-natal life. Using endothelial cells isolated from the mammary glands of the same mouse models, the project will also how these two integrins co-operate to regulate endothelial cell behavior in vitro.