Dlx homeobox gene control of mammalian limb and craniofacial development

The Dlx homeobox gene family is of ancient origin and crucial for embryonic development in invertebrates and vertebrates. The Dlx proteins are thought to function as DNA-binding transcriptional regulators, likely controlling large numbers of downstream effector genes. In mammals gene expression analysis of the six members of the Dlx gene family has been demonstrated in the nervous system, neural crest derivatives, branchial arches, and developing appendages. Through genetic approaches the Dlx genes have been implicated in patterning and development of the brain, craniofacial structures, and the axial and appendicular skeleton. Substantial functional redundancy within the Dlx gene family has prevented the analysis of single gene mutations from demonstrating the full developmental control exerted by the Dlx proteins. Here, we will discuss data from recent combined loss and gain-of-function genetic mutations, which have given greater insight into the role of Dlx homeobox genes in craniofacial, limb, and bone development.