Dissecting Dlx5- and Dlx6-mediated regulation of limb chondrogenesis: characterization of functional domains
In the early limb bud, 'Dlx5' and 'Dlx6', members of the 'Dlx' homeobox gene family, are expressed in condensed mesenchymal cells that differentiate into chondrocytes. Analyses of 'Dlx5' and compound 'Dlx5'/'6' mutant mice reveal that 'Dlx5' and 'Dlx6' positively regulate chondrocyte differentiation in a functionally redundant manner. We misexpressed 'Dlx5' and 'Dlx6' in chicken embryo limb bud mesenchymal cells both 'in vitro' and 'in vivo ' to map the functional domains of their chondrogenic stimulatory function. The amino-terminal domain of Dlx5 was required for its chondrogenic stimulatory function. In contrast to Dlx5, both the amino- and carboxy-terminal domains of Dlx6 were required for this conserved function. Results of the functional domain mapping of Dlx5 'in vivo' were consistent with the in vitro data, and misexpression of 'Dlx5' or ' Dlx6 in vivo' resulted in reduced ossification of all skeletal elements in the wing.