Dlx genes are a highly conserved family of six different (Dlx1–6) homeo box-containing genes that share homology with distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. Dlx genes are expressed in spatially and temporally restricted patterns in craniofacial primordia, basal telencephalon and diencephalon, and in distal regions of extending appendages, including the limb and the genital bud. The differential expression of Dlx influences patterning, morphogenesis and histogenesis in these tissues. The Dlx gene products can activate transcription and are localized primarily to the nucleus, although Dlx-5 can be found in the cytoplasm. Dlx proteins influence different stages of proper tissue development, including patterning of the orofacial skeleton (craniofacial ectomesenchyme) and differentiation of structures within and between teeth.