Epithelial cell integrin β1 is required for developmental angiogenesis in the pituitary gland.
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.
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093; kscully@ucsd.edu mrosenfeld@ucsd.edu.|Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Kathleen M
KM
Scully
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.|Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093.|Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92093.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093.
Dorota
D
Skowronska-Krawczyk
Shiley Eye Institute, Department of Ophthalmology, University of California, San Diego, La Jolla, CA 92093.|Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093.
Michal
M
Krawczyk
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.|Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Daria
D
Merkurjev
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093.|Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Havilah
H
Taylor
EMD Millipore, Temecula, CA 92590.
Antonia
A
Livolsi
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724.
Jessica
J
Tollkuhn
Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756.
Radu V
RV
Stan
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093; kscully@ucsd.edu mrosenfeld@ucsd.edu.|Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
Michael G
MG
Rosenfeld
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002454:Cell Differentiation; D047108:Embryonic Development / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D019426:Integrases / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000378:metabolism; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D010902:Pituitary Gland / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013997:Time Factors; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
D019012:Integrin beta1; D051761:Paired Box Transcription Factors; D042582:Vascular Endothelial Growth Factor C; C101485:homeobox protein PITX1; C045073:Cre recombinase; D019426:Integrases
angiogenesis; integrin β1; mice; pituitary gland