AP-2{alpha} and AP-2{beta} cooperatively orchestrate homeobox gene expression during branchial arch patterning [RESEARCH ARTICLE]

Eric Van Otterloo, Hong Li, Kenneth L. Jones, and Trevor Williams

The evolution of a hinged moveable jaw with variable morphology is considered a major factor behind the successful expansion of the vertebrates. DLX homeobox transcription factors are critical to establish the positional code that patterns the mandible, maxilla and intervening hinge domain, but how these genes are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2a and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning. In the absence of these two genes the hinge domain is lost and there are alterations in the size and patterning of the jaws correlating with dysregulation of homeobox gene expression, with reduced levels of Emx, Msx and Dlx paralogs accompanied by an expansion of Six1. Moreover, detailed analysis of morphological features and gene expression changes indicate significant overlap with various compound Dlx mutants. Together, these findings reveal that the AP-2 genes have a major function in mammalian neural crest development, influencing patterning of the craniofacial skeleton via the DLX-code, a result that has implications for vertebrate facial evolution as well as for human craniofacial disorders.

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