Epithelial cell integrin beta1 is required for developmental angiogenesis in the pituitary gland

Scully, K. M., Skowronska-Krawczyk, D., Krawczyk, M., Merkurjev, D., Taylor, H., Livolsi, A., Tollkuhn, J., Stan, R. V., Rosenfeld, M. G. (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)

URL: https://www.ncbi.nlm.nih.gov/pubmed/27810956
DOI: 10.1073/pnas.1614970113

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 Deposited: 15 Nov 2016 16:04
Last Modified: 10 Jan 2017 20:54
PMCID: PMC5127350
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33889

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