Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.

TGFβ 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 TGFβ receptor (Tgfbr2) specifically in...

Full description

Saved in:
Bibliographic Details
Main Authors: Kathleen R Allinson, Hye Shin Lee, Marcus Fruttiger, Joseph H McCarty, Helen M Arthur
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0039336&type=printable
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849330553117999104
author Kathleen R Allinson
Hye Shin Lee
Marcus Fruttiger
Joseph H McCarty
Helen M Arthur
author_facet Kathleen R Allinson
Hye Shin Lee
Marcus Fruttiger
Joseph H McCarty
Helen M Arthur
author_sort Kathleen R Allinson
collection DOAJ
description TGFβ 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 TGFβ 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 TGFβ 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, TGFβ 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.
format Article
id doaj-art-c8dfbef68226485da1dd33f33d6890de
institution Kabale University
issn 1932-6203
language English
publishDate 2012-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj-art-c8dfbef68226485da1dd33f33d6890de2025-08-20T03:46:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3933610.1371/journal.pone.0039336Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.Kathleen R AllinsonHye Shin LeeMarcus FruttigerJoseph H McCartyHelen M ArthurTGFβ 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 TGFβ 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 TGFβ 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, TGFβ 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0039336&type=printable
spellingShingle Kathleen R Allinson
Hye Shin Lee
Marcus Fruttiger
Joseph H McCarty
Helen M Arthur
Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
PLoS ONE
title Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
title_full Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
title_fullStr Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
title_full_unstemmed Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
title_short Endothelial expression of TGFβ type II receptor is required to maintain vascular integrity during postnatal development of the central nervous system.
title_sort endothelial expression of tgfβ type ii receptor is required to maintain vascular integrity during postnatal development of the central nervous system
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0039336&type=printable
work_keys_str_mv AT kathleenrallinson endothelialexpressionoftgfbtypeiireceptorisrequiredtomaintainvascularintegrityduringpostnataldevelopmentofthecentralnervoussystem
AT hyeshinlee endothelialexpressionoftgfbtypeiireceptorisrequiredtomaintainvascularintegrityduringpostnataldevelopmentofthecentralnervoussystem
AT marcusfruttiger endothelialexpressionoftgfbtypeiireceptorisrequiredtomaintainvascularintegrityduringpostnataldevelopmentofthecentralnervoussystem
AT josephhmccarty endothelialexpressionoftgfbtypeiireceptorisrequiredtomaintainvascularintegrityduringpostnataldevelopmentofthecentralnervoussystem
AT helenmarthur endothelialexpressionoftgfbtypeiireceptorisrequiredtomaintainvascularintegrityduringpostnataldevelopmentofthecentralnervoussystem