| Summary: | Congenital cardiovascular malformation is a common birth defect incorporating abnormalities of the outflow tract and aortic arch arteries, and mice deficient in the transcription factor <i>AP-2α</i> (<i>Tcfap2a</i>) present with complex defects affecting these structures. AP-2α is expressed in the pharyngeal surface ectoderm and neural crest at mid-embryogenesis in the mouse, but the precise tissue compartment in which <i>AP-2α</i> is required for cardiovascular development has not been identified. In this study we describe the fully penetrant <i>AP-2α</i> deficient cardiovascular phenotype on a C57Bl/6J genetic background and show that this is associated with increased apoptosis in the pharyngeal ectoderm. Neural crest cell migration into the pharyngeal arches was not affected. Cre-expressing transgenic mice were used in conjunction with an <i>AP-2α</i> conditional allele to examine the effect of deleting <i>AP-2α</i> from the pharyngeal surface ectoderm and the neural crest, either individually or in combination, as well as the second heart field. This, surprisingly, was unable to fully recapitulate the global <i>AP-2α</i> deficient cardiovascular phenotype. The outflow tract and arch artery phenotype was, however, recapitulated through early embryonic Cre-mediated recombination. These findings indicate that <i>AP-2α</i> has a complex influence on cardiovascular development either being required very early in embryogenesis and/or having a redundant function in many tissue layers.
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