Early Embryonic Expression of <i>AP-2α</i> Is Critical for Cardiovascular Development

• Main Authors: Amy-Leigh Johnson, Jürgen E. Schneider, Timothy J. Mohun, Trevor Williams, Shoumo Bhattacharya, Deborah J. Henderson, Helen M. Phillips, Simon D. Bamforth
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Journal of Cardiovascular Development and Disease
• Subjects: transcription factor AP-2α; cardiovascular development; outflow tract; pharyngeal arch artery; neural crest cell; pharyngeal ectoderm
• Online Access: https://www.mdpi.com/2308-3425/7/3/27

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.