Neural Crest Migration and Mouse Models of Congenital Heart Disease

Congenital heart disease is common, affecting nearly1% of live births. Perhaps one-third of the cases of congenital heart disease involve abnormal morphogenesis ofthe outflow tract of the heart and/or abnormal patterningof the great vessels (Driscoll 1994; Goldmuntz et al.1998). The development of these structures is influencedby migrating neural crest cells that arise from the dorsalneural tube and populate the pharyngeal arches and theheart (Kirby et al. 1983). Ablation studies in chick embryos suggest that neural crest migration defects can result in congenital heart disease. Recently, however, analyses of a series of mouse models with genetic forms ofcongenital heart disease that resemble human diseasesuggest that migration defects are uncommon. Newly developed molecular markers and fate-mapping techniquessuggest that functional defects of post-migratory neuralcrest cause some forms of common structural cardiovascular disorders. These defects can be cell autonomous orcan arise from defects in cells surrounding the neuralcrest migration pathways...