Endoglin plays distinct roles in vascular smooth muscle cell recruitment and regulation of arteriovenous identity during angiogenesis

ML Mancini, A Terzic, BA Conley… - … dynamics: an official …, 2009 - Wiley Online Library
ML Mancini, A Terzic, BA Conley, LH Oxburgh, T Nicola, CPH Vary
Developmental dynamics: an official publication of the American …, 2009Wiley Online Library
Blood vessel formation is a multi‐step process. Endoglin is a TGFβ coreceptor required for
angiogenesis. Endoglin null embryos exhibit a loss of arteriovenous identity and defective
vascular smooth muscle cell (vSMC) recruitment. Haploinsufficiency of endoglin results in
Hereditary Hemorrhagic Telangiectasia (HHT), characterized by a loss of arteriovenous
identity and aberrant vSMC incorporation in fragile vessels. We explored a cell‐autonomous
role for endoglin in endothelial and vSMCs during angiogenesis by conditionally activating …
Abstract
Blood vessel formation is a multi‐step process. Endoglin is a TGFβ coreceptor required for angiogenesis. Endoglin null embryos exhibit a loss of arteriovenous identity and defective vascular smooth muscle cell (vSMC) recruitment. Haploinsufficiency of endoglin results in Hereditary Hemorrhagic Telangiectasia (HHT), characterized by a loss of arteriovenous identity and aberrant vSMC incorporation in fragile vessels. We explored a cell‐autonomous role for endoglin in endothelial and vSMCs during angiogenesis by conditionally activating endoglin expression in wild type or endoglin null embryos using either smooth muscle (SM22αcre) or endothelial cell (Tie2cre) promoters to partially rescue vSMC recruitment to the dorsal aorta. Examination of endoglin null embryos revealed ectopic arterial expression of the venous‐specific marker COUPTFII. Endoglin re‐expression in endothelial cells restored normal COUPTFII expression. These results suggested that endoglin plays distinct and cell‐autonomous roles in vSMC recruitment and arteriovenous specification via COUPTFII in angiogenesis that may contribute to HHT. Developmental Dynamics 238:2479–2493, 2009. © 2009 Wiley‐Liss, Inc.
Wiley Online Library