Homeobox genes of the Distal-less family have been identified in virtually all metazoan groups where they play roles in the ontogeny of these animals. The vertebrate Distal-less related genes (Dlx genes) are thought to have arisen as a result of a tandem gene duplication event followed by a number of larger genomic scale duplications and thus represent an interesting model with which to study the evolution of clustered gene families. Dlx genes are involved in the development of the forebrain, branchial arches, sensory organs, and limbs. Here we describe the current state of knowledge of the Dlx genes in terms of their developmental expression, how this expression is regulated and how the products of these genes function, once expressed. We highlight a number of recent studies that have shed light on the transcriptional regulation of this gene family. These findings have not only contributed to our understanding of the selective pressures involved in the maintenance of familial gene clustering in genomes, but also to our understanding of how genes may diverge in function during the course of evolution as a result of divergence of regulatory mechanisms.
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