Epithelial Cell Integrin Β1 is Required for Developmental Angiogenesis in the Pituitary Gland

Authors

Kathleen M. Scully, University of California, San Diego
Dorota Skowronska-Krawczyk, University of California, San Diego
Michal Krawczyk, University of California, San Diego
Daria Merkurjev, University of California, San Diego
Havilah Taylor, University of California, San Diego
Antonia Livolsi, EMD Millipore, Temecula
Jessica Tollkuhn, Cold Spring Harbor Laboratory
Radu V. Stan, Dartmouth College
Michael G. Rosenfeld, University of California, San Diego

Document Type

Article

Publication Date

9-19-2016

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Department

Geisel School of Medicine

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 β1 in embryonic pituitary epithelial cells is required for angiogenesis in the developing mouse pituitary gland. Deletion of pituitary epithelial integrin β1 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 β1 was associated with a complete absence of vasculature in the pituitary gland at birth. Within pituitary epithelial cells, integrin β1 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 β1 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.

DOI

10.1073/pnas.1614970113

Dartmouth Digital Commons Citation

Scully, Kathleen M.; Skowronska-Krawczyk, Dorota; Krawczyk, Michal; Merkurjev, Daria; Taylor, Havilah; Livolsi, Antonia; Tollkuhn, Jessica; Stan, Radu V.; and Rosenfeld, Michael G., "Epithelial Cell Integrin Β1 is Required for Developmental Angiogenesis in the Pituitary Gland" (2016). Dartmouth Scholarship. 2686.
https://digitalcommons.dartmouth.edu/facoa/2686