Cardiac Neural Crest and Congenital Heart Defects

Abstract

Congenital heart defects (CHD) result from abnormal morphogenesis of the embryonic cardiovascular system and usually involve defects in specific structural components of the developing heart and vessels. Decades of research in molecular embryology have suggested that multiple distinct cell lineages give rise to the cardiovascular system. Neural crest cells (NCC) are pluripotent cells that delaminate from the dorsal neural tube and migrate widely throughout the body as mesenchymal cells. A subregion of the cranial NCC originating between the otocyst and somite 3 is called the “cardiac NCC” that migrate into the third, fourth, and sixth pharyngeal arches and the cardiac outflow tract. They contribute to the remodeling of the six pairs of bilaterally symmetric pharyngeal arch arteries that eventually results in formation of the aortic arch system. In addition, they also form the septum of the outflow tract that divides the embryonic single truncus arteriosus into the aortic and the pulmonary trunk. Recently, a new population of myocardial precursor cells in pharyngeal mesoderm anterior to the early heart tube was discovered and named the “second heart field (SHF)“. Reciprocal signaling between cardiac NCC and cells originated from the SHF are essential for the development of the outflow tract and the aortic arch system. Discovery of the SHF has provided important implications for the interpretation of the cardiac outflow tract development and new insights into the morphogenesis of CHD.