CRANIOFACIAL MORPHOGENESIS--AP-2 ALPHA

Brigham And Women'S Hospital, Boston MA

Investigators

Linked publications & trials

Abstract

Craniofacial development involves complex coordination of pattern formation, cell migration, cellular differentiation, cell to cell signaling, and cell death. Disruption of any of these processes can result in abnormal facial development. The transcription factor AP-2alpha has either been implicated in or shown to directly affect each of the above processes. Mice bearing a homozygous disruption of the AP-2alpha locus die perinatally and display multiple developmental defects including severe craniofacial malformation. This initiative will generate a mouse model system in which the AP-2alpha gene disruption is localized to the face. Studies on this novel mouse model will allow dissection of cell lineages contributing to the severe defects observed in the head of the AP-2alpha null mouse and will uncover the cellular processes specifically affected by AP-2alpha in the facial mesenchyme. In addition this initiative will augment our understanding of the molecular mechanisms behind the cellular processes involved in facial morphogenesis. Finally, a face-specific AP-2alpha knockout mouse is likely to be a valuable model for understanding human birth defects because disruption of the AP-2alpha locus has been correlated with severe orofacial clefting in humans.