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

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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.