期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：47
页码：13408-13413
DOI：10.1073/pnas.1614970113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceDuring embryogenesis, a dense vascular network develops in the pituitary gland through the process of angiogenesis. In tandem, pituitary gland precursor cells differentiate into hormone-producing cells that will rely on the vasculature to carry out regulated endocrine function. Our data show that expression of the cell surface adhesion molecule, integrin {beta}1, in the epithelial-derived precursor cells is required for development of the vasculature and coordinated terminal differentiation of endocrine cells. As a key component of the vertebrate neuroendocrine system, the pituitary gland relies on the progressive and coordinated development of distinct hormone-producing cell types and an invading vascular network. The molecular mechanisms that drive formation of the pituitary vasculature, which is necessary for regulated synthesis and secretion of hormones that maintain homeostasis, metabolism, and endocrine function, remain poorly understood. Here, we report that expression of integrin {beta}1 in embryonic pituitary epithelial cells is required for angiogenesis in the developing mouse pituitary gland. Deletion of pituitary epithelial integrin {beta}1 before the onset of angiogenesis resulted in failure of invading endothelial cells to recruit pericytes efficiently, whereas deletion later in embryogenesis led to decreased vascular density and lumen formation. In both cases, lack of epithelial integrin {beta}1 was associated with a complete absence of vasculature in the pituitary gland at birth. Within pituitary epithelial cells, integrin {beta}1 directs a large transcriptional program that includes components of the extracellular matrix and associated signaling factors that are linked to the observed non-cell-autonomous effects on angiogenesis. We conclude that epithelial integrin {beta}1 functions as a critical and canonical regulator of developmental angiogenesis in the pituitary gland, thus providing insight into the long-standing systems biology conundrum of how vascular invasion is coordinated with tissue development.
