Poster Sessions

DEV-6

Olivier Duverger

O. Duverger, N. Gentile, K. Maddox, A. Bartels, M. Morasso

Conditional Ablation of Dlx3 in Cranial Neural Crest-derived Cells Results in Abnormal Development of Hair, Teeth and Craniofacial Bone

During embryogenesis, the homeodomain transcription factor, Dlx3, is involved in the development of structures derived from epithelial-mesenchymal interactions such as hair and teeth, as well as in bone (craniofacial and appendicular). In humans, a frameshift mutation in the coding sequence of DLX3 results in an ectodermal dysplasia known as Tricho-Dento-Osseous (TDO) syndrome. TDO patients have defects in hair, teeth and bone. At E11.5, Dlx3 is expressed in post-migratory cranial neural crest (CNC) that are known to contribute to hair, teeth and craniofacial bone formation. In order to assess the role of Dlx3 in CNC, we generated mice lacking Dlx3 in all CNC-derived tissues, using Wnt1-cre and Dlx3-floxed mice. These mice exhibit visible hair defects with a disheveled coat, kinky vibrissae and sparse hair on the head. Analysis of the composition of the coat revealed a change in the proportion and structure of specific hair types. Mutant mice also exhibit major tooth defects: their incisors are small and underdeveloped as compared to their wild-type littermates. Histological analysis of the teeth revealed a dramatic hypoplasia of the dentine that is totally absent on the labial part of the incisors. The structure, size and bone mineral density of the skull are also affected. These data demonstrate that the expression of Dlx3 in CNC-derived cells is essential for normal development of the three structures affected in TDO syndrome.