HAND proteins: molecular mediators of cardiac development and congenital heart disease.

Congenital heart defects are the clinical manifestation of anomalies in embryonic cardiac development. Such defects occur in distinct regions or chambers of the heart. A molecular framework in which to consider cardiac development and congenital heart disease in a segmental fashion has begun to emerge. dHAND and eHAND are two related basic helix-loop-helix transcription factors that are expressed in a complementary fashion in the developing right and left ventricles, respectively. They are also expressed in the neural crest-derived cardiac outflow tract and aortic arch arteries. Targeted mutations of dHAND and eHAND in mice have revealed novel pathways of organogenesis in mesodermal and neural crest derivatives. dHAND mutants exhibit hypoplasia of the right ventricle, branchial arches, and aortic arch arteries. The distinct nature of cardiac defects in dHAND mutants provides an entry into dissecting molecular pathways governing morphogenesis of specific components of the heart. Congenital heart disease is considered as a defect in segmental development of the heart and the role of dHAND and eHAND in regulating such developmental pathways in normal and abnormal cardiogenesis is examined.