Direct evidence of allele equivalency at the Dlx5/6 locus

Abstract

The retention of paralogous regulatory genes is a vertebrate hallmark and likely underpinned vertebrate origins. Dlx genes belong to a family of paralogous transcription factors whose evolutionary history of gene expansion and divergence is apparent from the gene synteny, shared exon-intron structure, and coding sequence homology found in extant vertebrate genomes. Dlx genes are expressed in a nested combination within the first pharyngeal arch and knockout studies in mice clearly point to a "Dlx code" that operates to define maxillary and mandibular position in the first arch. The nature of that code is not yet clear; an important goal for understanding Dlx gene function in both patterning and differentiation lies in distinguishing functional inputs that are paralog-specific (a qualitative model) versus Dlx family-generic (a quantitative model) and, in the latter case, the relative contribution made by each paralog. Here, multiple developmental deficiencies were identified in derivatives of the first pharyngeal arch in neonatal Dlx5/6(+/-) mice that resembled those seen in either paralog-specific null mutants. These data clearly demonstrate a substantial degree of allele equivalency and support a quantitative model of Dlx function during craniofacial morphogenesis. genesis 54:272-276, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: Dlx5; Dlx6; craniofacial morphogenesis; functional equivalence; paralog; patterning; pharyngeal arch; transcription factor.