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Endothelial Expression of TGF beta Type II Receptor Is Required to Maintain Vascular Integrity during Postnatal Development of the Central Nervous System

Lookup NU author(s): Kathleen Allinson, Professor Helen Arthur

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Abstract

TGF beta signalling in endothelial cells is important for angiogenesis in early embryonic development, but little is known about its role in early postnatal life. To address this we used a tamoxifen inducible Cre-LoxP strategy in neonatal mice to deplete the TypeII TGF beta receptor (Tgfbr2) specifically in endothelial cells. This resulted in multiple micro-haemorrhages, and glomeruloid-like vascular tufts throughout the cerebral cortices and hypothalamus of the brain as well as in retinal tissues. A detailed examination of the retinal defects in these mutants revealed that endothelial adherens and tight junctions were in place, pericytes were recruited and there was no failure of vascular smooth muscle differentiation. However, the deeper retinal plexus failed to form in these mutants and the angiogenic sprouts stalled in their progress towards the inner nuclear layer. Instead the leading endothelial cells formed glomerular tufts with associated smooth muscle cells. This evidence suggests that TGF beta signalling is not required for vessel maturation, but is essential for the organised migration of endothelial cells as they begin to enter the deeper layers of the retina. Thus, TGF beta signalling is essential in vascular endothelial cells for maintaining vascular integrity at the angiogenic front as it migrates into developing neural tissues in early postnatal life.


Publication metadata

Author(s): Allinson KR, Lee HS, Fruttiger M, McCarty J, Arthur HM

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2012

Volume: 7

Issue: 6

Print publication date: 26/06/2012

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0039336

DOI: 10.1371/journal.pone.0039336


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