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Congenital heart defects (CHD) are the most common type of human birth defect and result in significant mortality worldwide. Despite numerous epidemiologic studies in the past decades, few genetic causes have been identified until recently. CHD result from abnormal morphogenesis of the systematic cardiovascular construction during development. Recent advances in molecular embryology, including the discovery of a new source of cardiac progenitor cells termed the second heart field (SHF), have revealed that the heart arises from multiple distinct embryonic origins. Cells derived from the SHF contribute to the development of the cardiac outflow tract, together with the other progenitor cell lineage called cardiac neural crest cells. Numerous cardiac transcription factors regulate these progenitor cells during heart development. Elucidation of the transcriptional network for these cardiac progenitor cells is essential for further understanding cardiac development and providing new insights into the morphogenesis of CHD. This review outlines the recent discoveries of the molecular embryology of the normal heart and the genetic basis of CHD.

A Decade of Advances in the Molecular Embryology and Genetics Underlying Congenital Heart Defects