Premium
The Type III Transforming Growth Factor β Receptor ( tgfbr3 ) is Required for Coronary Vasculogenesis and Embryonic Viability
Author(s) -
Compton Leigh A.,
Potash Dru A.,
Mundell Nathan A.,
Brown Chris B.,
Barnett Joey V.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a22-c
Subject(s) - vasculogenesis , mesenchyme , biology , transforming growth factor , embryonic stem cell , receptor , microbiology and biotechnology , medicine , anatomy , endocrinology , stem cell , embryo , gene , genetics , progenitor cell
Transforming Growth Factor Beta (TGFβ) Receptor III (TBRIII) or betaglycan binds all three TGFβ ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the Type I and Type II receptors (TBRI, TBRII). TBRIII can facilitate signaling via TBRI/TBRII but also has been suggested to play a unique and nonredundant role in TGFβ signaling. Targeted deletion of the gene encoding mouse TBRIII, tgfbr3 , revealed a unique requirement for tgfbr3 during development of the coronary vessels. tgfbr3 null mice die around 14.5 dpc with fewer PECAM‐positive coronary vessels and an apparent absence of remodeled vessels while other vascular beds appeared intact. Despite the paucity of coronary vessels, both right and left coronary ostia formed along the aortic wall. Analysis of earlier developmental stages revealed profound defects in the interaction of the proepicardium (PE) with the myocardium and subsequent formation of the epicardium (EP). At 13.5 dpc these defects include the continued presence of the PE and PE‐derived vesicles, an irregular and hypercellular EP with excess subepicardial mesenchyme and a thin compact zone myocardium. tgfbr3 null mice also displayed other defects in coronary development including dysmorphic and distended vessels along the AV groove, subepicardial hemorrhage and multiple, large, persistent blood islands. These data demonstrate a requirement for tgfbr3 during coronary vasculogenesis that is essential for embryonic viability. NIH HL67105; Vanderbilt MSTP 5 T32 GM07347