Abstract
Congenital heart disease （CHD）occurs in nearly 1% of all live births and is the major cause of infant mortality and morbidity. Despite its clinical importance, the underlying genetic etiology of most CHD remains unknown because of the multi-factorial nature. As CHD results usually from abnormal morphogenesis in specific structural regions of the developing heart and vessels, an understanding of the individual modular steps in cardiovascular morphogenesis is particularly relevant to CHD. Transcription factors Nkx2.5/Csx and dHAND/Hand2 are together essential for ventricular morphogenesis. TBX1, a major genetic determinant of 22q11.2 deletion syndrome, regulates second heart field （SHF）cells during outflow tract development. Mutations of GATA6 result in outflow tract defects implicated in the interaction between the SHF and neural crest progenitors. Finally, intracellular calcium signaling redundantly mediated by three subtypes of IP3 receptors may play essential roles in region-specific development of the heart. Through the advance of molecular biology combined with human genetics, basic and clinical understanding of cardiovascular development and diseases have emerged. Elucidation of the mechanisms from gene to morphology would provide targets for prevention or genetic intervention of CHD as suggested in Professor Takao’s will.
