ROLE OF DLX-1 AND DLX-2 GENES IN PATTERNING OF THE MURINE DENTITION

The molecular events of odontogenic induction are beginning to be eluc idated, but until now nothing was known about the molecular basis of t he patterning of the dentition. A role for Dlx-1 and Dlx-2 genes in pa tterning of the dentition has been proposed with the genes envisaged a s participating in an 'odontogenic homeobox gene code' by specifying m olar development, This proposal was based on the restricted expression of the genes in molar ectomesenchyme derived from cranial neural cres t cells prior to tooth initiation. Mice with targeted null mutations o f both Dlx-1 and Dlx-2 homeobox genes do not develop maxillary molar t eeth but incisors and mandibular molars are normal, We have carried ou t heterologous recombinations between mutant and wild-type maxillary e pithelium and mesenchyme and show that the ectomesenchyme underlying t he maxillary molar epithelium has lost its odontogenic potential, Usin g molecular markers of branchial arch neural crest (Barx1) and commitm ent to chondrogenic differentiation (Sax9), we show that this populati on alters its fate from odontogenic to become chondrogenic, These resu lts provide evidence that a subpopulation of cranial neural crest is s pecified as odontogenic by Dlx-1 and Dlx-2 genes, Loss of function of these genes results in reprogramming of this population of ectomesench yme cells into chondrocytes. This is the first indication that the dev elopment of different shaped teeth at different positions in the jaws is determined by independent genetic pathways.