ROLE OF THE DLX HOMEOBOX GENES IN PROXIMODISTAL PATTERNING OF THE BRANCHIAL ARCHES - MUTATIONS OF DLX-1, DLX-2, AND DLX-1 AND -2 ALTER MORPHOGENESIS OF PROXIMAL SKELETAL AND SOFT-TISSUE STRUCTURES DERIVED FROMTHE FIRST AND 2ND ARCHES

The Dir homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous stu dy established that Dlx-2 is essential for development of proximal reg ions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and D lx-1 and -2 mutations provide additional evidence that the Dir genes r egulate proximodistal patterning of the branchial arches. This analysi s also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 i n craniofacial development. furthermore, mice lacking both Dlx-1 and - 2 have unique abnormalities, including the absence of maxillary molars . Dlx-1 and -2 are expressed in the proximal and distal first and seco nd arches, yet only the proximal regions are abnormal. The nested expr ession patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a mo del that predicts the region-specific requirements for each gene. Fina lly, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more prim itive vertebrates. (C) 1997 Academic Press.