AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning

• Published in: Development (Cambridge) Vol. 145; no. 2; p. dev157438
• Main Authors: Van Otterloo, Eric, Li, Hong, Jones, Kenneth L, Williams, Trevor
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15.01.2018
• Subjects: Animals; Body Patterning - physiology; Branchial Region - cytology; Branchial Region - embryology; Dlx protein; Evolution; Gene expression; Gene Expression Regulation, Developmental - physiology; Homeobox; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; Jaw; Mandible; Maxilla; Mice; Mice, Transgenic; Neural crest; Neural Crest - cytology; Neural Crest - metabolism; Pattern formation; SIX gene family; Transcription Factor AP-2 - genetics; Transcription Factor AP-2 - metabolism; Transcription factors; Homeobox; DLX; TFAP2; Mandible; Pharyngeal arch; Branchial arch; AP-2; Neural crest; Maxilla
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.157438

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 crucial for establishing the positional code that patterns the mandible, maxilla and intervening hinge domain, but how the genes encoding these proteins are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2α and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning. In the absence of these two proteins, 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 expression. Moreover, detailed analysis of morphological features and gene expression changes indicate significant overlap with various compound Dlx gene 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, an effect that has implications for vertebrate facial evolution, as well as for human craniofacial disorders.