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First published online 18 October 2006
doi: 10.1242/dev.02597

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Tgfß signaling is required for atrioventricular cushion mesenchyme remodeling during in vivo cardiac development

¹ Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt Children's Hospital
² Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
³ Division of Genetic and Translational Medicine, Department of Genetics, The University of Alabama at Birmingham, Kaul 768, 720 20th Street S., Birmingham, AL 35294, USA.
⁴ Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁵ Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

^* Author for correspondence (e-mail: scott.baldwin{at}Vanderbilt.edu)

Accepted 30 August 2006

The transforming growth factorß (Tgfß) signaling pathway plays crucial roles in many biological processes. To understand the role(s) of Tgfß 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 Tgfß signaling is required for the proper remodeling of the atrioventricular canal and for cardiac looping, and that perturbation in Tgfß 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.

Key words: Tgfß, Cardiogenesis, AV remodeling, DILV, Congenital heart disease, Mouse

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