Developmental functions of the Distal-less/Dlx homeobox genes

Distal-less is the earliest known gene specifically expressed in developing insect limbs; its expression is maintained throughout limb development. The homeodomain transcription factor encoded by Distal-less is required for the elaboration of proximodistal pattern elements in Drosophila limbs and can initiate proximodistal axis formation when expressed ectopically. Distal-less homologs, the Dlx genes, are expressed in developing appendages in at least six phyla, including chordates, consistent with requirements for Dlx function in normal appendage development across the animal kingdom. Recent work implicates the Dlx genes of vertebrates in a variety of other developmental processes ranging from neurogenesis to hematopoiesis. We review what is known about the invertebrate and vertebrate Dll/Dlx genes and their varied roles during development. We propose revising the vertebrate nomenclature to reflect phylogenetic relationships among the Dlx genes.