This early expression of Dlx2 in the mesenchyme in the proximal, future molar regions is consistent with a role for the Dlx genes in dental patterning resulting from its mesenchymal expression domain, as predicted in the odontogenic homeobox

The distal-less family of homeobox genes contains six members, Dlx1, Dlx2, Dlx3, Dlx5, Dlx6 and Dlx7, arranged in convergent pairs within the genome of mammals. Both genes of a given pair (Dlx1 and Dlx2, Dlx3 and Dlx7, Dlx5 and 6) have been shown to have similar domains of expression (Qiu et al., 1997). Dlx1 and Dlx2 are expressed in the epithelium and mesenchyme of the maxillary and mandibular divisions of the first branchial arch in similar domains. Likewise, Dlx5 and Dlx6 share very similar expression domains and their expression patterns in the mandibular division of the first branchial arch are similar to those of Dlx1 and Dlx2, although they are not expressed in the maxillary division of the first arch (Qiu et al., 1997). The Dlx genes had been suggested to be involved in a homeobox code patterning the ectomesenchyme of the first arch with respect to tooth development (Sharpe, 1995). Loss of function of Dlx1 and Dlx2 results in failure of development of upper molars (Thomas et al., 1997), supporting their role in odontogenic patterning. The effect on the upper jaw only, with mandibular molars developing normally, has been explained by the expression of other Dlx genes, such as Dlx5 and Dlx6 in the mandible, compensating for the loss of Dlx1 and Dlx2 in mandibular molar development (Qiu et al., 1997; Thomas et al., 1997). Prior to the initiation of tooth development, Dlx1 and Dlx2 are expressed in the proximal mesenchyme of both the maxillary and mandibular divisions of the first arch (Thomas and Sharpe, 1998). This mesenchyme contributes to the development of molar teeth. At this stage the proximal epithelium does not express these Dlx genes, but epithelial expression is present towards the distal tips of the maxillary and mandibular divisions of the first arch, that is, in epithelium not overlying Dlx1 and Dlx2 expressing mesenchyme. Thus, expression of these two genes resides in distinct domains in the epithelium and mesenchyme; their domains of expression abut approximately midway along the arches (Bulfone et al., 1993; Qiu et al., 1997; Thomas and Sharpe, 1998) (Fig. 1F-I). This early expression of Dlx2 in the mesenchyme in the proximal, future molar regions is consistent with a role for the Dlx genes in dental patterning resulting from its mesenchymal expression domain, as predicted in the odontogenic homeobox code (Thomas and Sharpe, 1998; Sharpe, 1995). This has been confirmed by tissue recombination experiments using Dlx1/Dlx2 mutant mice in which mutant epithelium 217 Development 127, 217-224 (2000) Printed in Great Britain © The Company of Biologists Limited 2000 DEV2450