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Critical Functions of TGFbeta Signaling during Atrioventricular Cushion Remodeling
Author(s) -
Jiao Kai
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.a226-d
Subject(s) - mesenchyme , atrioventricular canal , microbiology and biotechnology , atrioventricular cushions , endocardium , transforming growth factor , biology , in vivo , mesoderm , transforming growth factor beta , signal transduction , tgf beta signaling pathway , chemistry , embryonic stem cell , anatomy , embryo , medicine , genetics , gene , heart disease
The Transforming‐Growth‐Factorβ (TGFβ) signaling pathway plays critical roles in many biological processes. To understand the role(s) of TGFβ signaling during cardiogenesis in vivo and to overcome the functional redundancy of TGFβ ligands, we inactivated T β RII , which encodes the only known type II receptor for TGFβ1–3 ligands, in either the myocardium or the endothelium using a Cre/loxp system. Our results show that T β RII in the myocardium is dispensable for cardiogenesis of most embryos. Contrary to results obtained from previous in vitro collagen gel assays, inactivation of T β RII in the endocardium does not inhibit atrioventricular cushion mesenchyme formation, excluding its essential role in Epithelium‐Mesenchyme‐Transformation (EMT) in vivo . We further demonstrate that TGFβ signaling is required for proper remodeling of the atrioventricular canal (AVC) and cardiac looping, and perturbation causes the double‐inlet‐left‐ventricle (DILV) defect. To the best of our knowledge, this is the first genetic model with DILV. Further characterization of this unique model suggests a unique cellular mechanism for DILV.