title: Endoglin plays distinct roles in vascular smooth muscle cell recruitment and regulation of arteriovenous identity during angiogenesis.
abstract: Blood vessel formation is a multi-step process. Endoglin is a TGFbeta 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 (SM22alphacre) 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.
authors.affiliation: Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Mancini
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Terzic
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Conley
authors.forename: Leif H
authors.initials: LH
authors.lastname: Oxburgh
authors.forename: Teodora
authors.initials: T
authors.lastname: Nicola
authors.forename: Calvin P H
authors.initials: CP
authors.lastname: Vary
mesh_terms: D000818:Animals; D001158:Arteries / Q000254:growth & development / Q000378:metabolism; D051837:COUP Transcription Factor II / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000378:metabolism; D000071063:Endoglin; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics / Q000378:metabolism; D014680:Veins / Q000254:growth & development / Q000378:metabolism; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D051837:COUP Transcription Factor II; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C497587:Nr2f2 protein, mouse; C051615:transgelin; D014841:von Willebrand Factor; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse
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