Signaling Pathways Involved in Cardiogenesis

Deepak Srivastava, Chulan Kwon

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


This chapter gives an overview on signaling pathways involved in cardiogenesis and congenital heart disease (CHD) considering different regions of the developing heart. The transcription factor Tbx1, which appears to be a cause of cardiac and craniofacial disorders in humans, is a major transcriptional regulator of the serum response factor (SRF), and is necessary for proper development of conotruncal myocardium and fibroblast growth factor secretion. Islet1 (Isl1), a transcription factor involved in pancreatic development, is also necessary for its development. The Wnt signals play a dynamic and critical role in regulating cardiac progenitors. Wnt signals are necessary to promote mesoderm formation, but subsequently need to be repressed in order for cardiac mesoderm to emerge. A discrete dorsalventral (DV) polarity is present in the primitive heart tube in addition to the AP segmentation. Congenital cardiac defects involving the cardiac outflow tract, aortic arch, ductus arteriosus, and proximal pulmonary arteries account for 20-30 percent of all CHD. This region of the heart undergoes extensive and rather complex morphogenetic changes, with reciprocal interactions between neural crest cells and the second heart field (SHF) and endoderm playing critical roles. Disruption of SHF development by mutation of genes such as Tbx1, Fgf8, and Isl1 results in defects similar to those observed with neural crest disruption, including persistent truncus arteriosus, malalignment of the outflow tract of the heart with the ventricular chambers, and ventricular septal defects. SHF-derived myocardial cells neighbor neural crest-derived cells and secrete growth factors in a Tbx1-dependent manner. Such growth factors influence neural crest cells, and reciprocal interactions between the SHF and neural crest-derived cells in the outflow tract are likely essential for normal development of heart.

Original languageEnglish (US)
Title of host publicationHandbook of Cell Signaling, Second Edition
Number of pages9
ISBN (Electronic)9780123741455
StatePublished - Jan 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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