Toggle Main Menu Toggle Search

Open Access padlockePrints

TGF beta Signaling and Congenital Heart Disease: Insights from Mouse Studies

Lookup NU author(s): Professor Helen ArthurORCiD, Dr Simon BamforthORCiD


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Transforming growth factor beta (TGF beta) regulates one of the major signaling pathways that control tissue morphogenesis. In vitro experiments using heart explants indicated the importance of this signaling pathway for the generation of cushion mesenchymal cells, which ultimately contribute to the valves and septa of the mature heart. Recent advances in mouse genetics have enabled in vivo investigation into the roles of individual ligands, receptors, and coreceptors of this pathway, including investigation of the tissue specificity of these roles in heart development. This work has revealed that (1) cushion mesenchyme can form in the absence of TGF beta signaling, although mesenchymal cell numbers may be misregulated; (2) TGF beta signaling is essential for correct remodeling of the cushions, particularly those of the outflow tract; (3) TGF beta signaling also has a role in ensuring accurate remodeling of the pharyngeal arch arteries to form the mature aortic arch; and (4) mesenchymal cells derived from the epicardium require TGF beta signaling to promote their differentiation to vascular smooth muscle cells to support the coronary arteries. In addition, a mouse genetics approach has also been used to investigate the disease pathogenesis of Loeys-Dietz syndrome, a familial autosomal dominant human disorder characterized by a dilated aortic root, and associated with mutations in the two TGF beta signaling receptor genes, TGFBR1 and TGFBR2. Further important insights are likely as this exciting work progresses. Birth Defects Research (Part A) 91:423-434, 2011. (C) 2011 Wiley-Liss, Inc.

Publication metadata

Author(s): Arthur HM, Bamforth SD

Publication type: Review

Publication status: Published

Journal: Birth Defects Research Part A: Clinical and Molecular Teratology

Year: 2011

Volume: 91

Issue: 6

Pages: 423-434

Print publication date: 28/04/2011

ISSN (print): 1542-0752

ISSN (electronic): 1542-0760



DOI: 10.1002/bdra.20794