The analyses of transgenic and knockout mice with perturbations in alpha 1 connexin (Cx43) function have revealed an important role for gap junctions in cardiac development. This likely involves the modulation of cardiac crest migration and function. Studies carried out with these mouse models suggest that clinically there may be a novel category of cardiac defects involving crest perturbations that do not include outflow septation defects, but rather involve more subtle defects in the pulmonary outflow tract.