Abstract
The transforming growth factorβ (Tgfβ) signaling pathway plays crucial roles in many biological processes. To understand the role(s) of Tgfβ signaling during cardiogenesis in vivo and to overcome the early lethality of Tgfbr2-/- embryos, we applied a Cre/loxp system to specifically inactivate Tgfbr2 in either the myocardium or the endothelium of mouse embryos. Our results show that Tgfbr2 in the myocardium is dispensable for cardiogenesis in most embryos. Contrary to the prediction from results of previous in vitro collagen gel assays, inactivation of Tgfbr2 in the endocardium does not prevent atrioventricular cushion mesenchyme formation, arguing against its essential role in epithelium-mesenchyme transformation in vivo. We further demonstrate that Tgfβ signaling is required for the proper remodeling of the atrioventricular canal and for cardiac looping, and that perturbation in Tgfβ signaling causes the double-inlet left ventricle (DILV) defect. Thus, our study provides a unique mouse genetic model for DILV, further characterization of which suggests a potential cellular mechanism for the defect.
Original language | English (US) |
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Pages (from-to) | 4585-4593 |
Number of pages | 9 |
Journal | Development |
Volume | 133 |
Issue number | 22 |
DOIs | |
State | Published - Nov 2006 |
Externally published | Yes |
Keywords
- AV remodeling
- Cardiogenesis
- Congenital heart disease
- DILV
- Mouse
- Tgfβ
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology