Scully, K. M., Skowronska-Krawczyk, D., Krawczyk, M., Merkurjev, D., Taylor, H., Livolsi, A., Tollkuhn, J., Stan, R. V., Rosenfeld, M. G. (November 2016) Epithelial cell integrin beta1 is required for developmental angiogenesis in the pituitary gland. Proc Natl Acad Sci U S A, 113 (47). pp. 13408-13413. ISSN 1091-6490 (Electronic)0027-8424 (Linking)
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Abstract
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 beta1 in embryonic pituitary epithelial cells is required for angiogenesis in the developing mouse pituitary gland. Deletion of pituitary epithelial integrin beta1 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 beta1 was associated with a complete absence of vasculature in the pituitary gland at birth. Within pituitary epithelial cells, integrin beta1 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 beta1 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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | angiogenesis integrin beta1 mice pituitary gland |
| Subjects: | diseases & disorders > cancer > angiogenesis organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > integrin |
| CSHL Authors: | |
| Communities: | CSHL labs > Tollkuhn lab |
| Depositing User: | Matt Covey |
| Date: | 3 November 2016 |
| Date Deposited: | 15 Nov 2016 16:04 |
| Last Modified: | 08 Nov 2017 20:01 |
| PMCID: | PMC5127350 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/33889 |
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