Ras-related signaling pathways in valve development: ebb and flow

Congenital heart defects affect ~1 in every 100 live births, and deficits in the formation of the mitral, tricuspid, and outflow tract valves account for 20–25% of all cardiac malformations. Mutations in genes that affect Ras signaling have been identified in individuals with congenital valve disease associated with Noonan syndrome and neurofibromatosis type 1. Dissection of Ras-related signaling pathways during valvulogenesis provides seminal insight into cellular and molecular mechanisms that contribute to congenital heart disease.