Early Embryonic Expression of AP-2α Is Critical for Cardiovascular Development

• Published in: Journal of cardiovascular development and disease 2020-07, Vol.7 (3), p.27
• Main Authors: Johnson, Amy-Leigh, Schneider, Jürgen E, Mohun, Timothy J, Williams, Trevor, Bhattacharya, Shoumo, Henderson, Deborah J, Phillips, Helen M, Bamforth, Simon D
• Format: Article
• Language: English
• Subjects: cardiovascular development; neural crest cell; outflow tract; pharyngeal arch artery; pharyngeal ectoderm; transcription factor AP-2α
• ISSN: 2308-3425; 2308-3425
• DOI: 10.3390/jcdd7030027

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 ( ) 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 is required for cardiovascular development has not been identified. In this study we describe the fully penetrant 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 conditional allele to examine the effect of deleting 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 deficient cardiovascular phenotype. The outflow tract and arch artery phenotype was, however, recapitulated through early embryonic Cre-mediated recombination. These findings indicate that has a complex influence on cardiovascular development either being required very early in embryogenesis and/or having a redundant function in many tissue layers.