NULL MUTATION OF DLX-2 RESULTS IN ABNORMAL MORPHOGENESIS OF PROXIMAL FIRST AND 2ND BRANCHIAL ARCH DERIVATIVES AND ABNORMAL DIFFERENTIATION IN THE FOREBRAIN

Genetic analysis of the development and evolution of the vertebrate he ad is at a primitive stage. Many homeo box genes, including the Distal -less family, are potential regulators of head development. To determi ne the function of DIx-2, we generated a null mutation in mice using g ene targeting. In homozygous mutants, differentiation within the foreb rain is abnormal and the fate of a subset of cranial neural crest cell s is respecified. The latter causes abnormal morphogenesis of the skel etal elements derived from the proximal parts of the first and second branchial arches. We hypothesize that the affected skull bones from th e first arch have undergone a transformation into structures similar t o those found in reptiles. These results show that Dlx-2 controls deve lopment of the branchial arches and the forebrain and suggests its rol e in craniofacial evolution.