Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption

Semaphorin 3C is a secreted member of the semaphorin gene family. To invest igate its function in vivo, we have disrupted the semaphorin 3C locus in mi ce by targeted mutagenesis. semaphorin 3C mutant mice die within hours afte r birth from congenital cardiovascular defects consisting of interruption o f the aortic arch and improper septation of the cardiac outflow tract. This phenotype is similar to that reported following ablation of the cardiac ne ural crest in chick embryos and resembles congenital heart defects seen in humans. Semaphorin 3C is expressed in the cardiac outflow tract as neural c rest cells migrate into it. Their entry is disrupted in semaphorin 3C mutan t mice. These data suggest that semaphorin 3C promotes crest cell migration into the proximal cardiac outflow tract.