Dlx5 regulates regional development of the branchial arches and sensory capsules

We report the generation and analysis of mice homozygous for a targeted del etion of the Dlx5 homeobox gene. Dlx5 mutant mice have multiple defects in craniofacial structures, including their ears, noses, mandibles and calvari a, and die shortly after birth. A subset (28%) exhibit exencephaly, Ectoder mal expression of Dlx5 is required for the development of olfactory and oti c placode-derived epithelia and surrounding capsules. The nasal capsules ar e hypoplastic (e.g, lacking turbinates) and, in most cases, the right side is more severely affected than the left. Dorsal otic vesicle derivatives (e .g. semicircular canals and endolymphatic duct) and the surrounding capsule , are more severely affected than ventral (cochlear) structures. Dlx5 is al so required in mandibular arch ectomesenchyme, as the proximal mandibular a rch skeleton is dysmorphic. Dlx5 may control craniofacial development in pa rt through the regulation of the goosecoid homeobox gene. goosecoid express ion is greatly reduced in Dlx5 mutants, and both goosecoid and Dlx5 mutants share a number of similar craniofacial malformations, Dlx5 may perform a g eneral role in skeletal differentiation, as exemplified by hypomineralizati on within the calvaria. The distinct focal defects within the branchial arc hes of the Dlx1, Dlx2 and Dlx5 mutants, along with the nested expression of their RNAs, support a model in which these genes have both redundant and u nique functions in the regulation of regional patterning of the craniofacia l ectomesenchyme.