PlexinA2 and semaphorin signaling during cardiac neural crest development

Classic studies using avian model systems have demonstrated that cardiac ne ural crest cells are required for proper development of the cardiovascular system. Environmental influences that perturb neural crest development caus e congenital heart defects in laboratory animals and in man. However, littl e progress has been made in determining molecular programs specifically reg ulating cardiac neural crest migration and function. Only recently have com plex transgenic tools become available that confirm the presence of cardiac neural crest cells in the mammalian heart. These studies have relied upon the use of transgenic mouse lines and fate-mapping studies using Cre recomb inase and neural crest-specific promoters. In this study, we use these tech niques to demonstrate that PlexinA2 is expressed by migrating and postmigra tory cardiac neural crest cells in the mouse. Plexins function as co-recept ors for semaphorin signaling molecules and mediate axon pathfinding in the central nervous system. We demonstrate that PlexinA2-expressing cardiac neu ral crest cells are patterned abnormally in several mutant mouse lines with congenital heart disease including those lacking the secreted signaling mo lecule Semaphorin 3C. These data suggest a parallel between the function of semaphorin signaling in the central nervous system and in the patterning o f cardiac neural crest in the periphery.