DISRUPTION OF THE HOXD-13 GENE INDUCES LOCALIZED HETEROCHRONY LEADINGTO MICE WITH NEOTENIC LIMBS

Vertebrate Hoxd genes are sequentially activated during the morphogene sis and pattern formation of the limb. Using the approach of gene disr uption via homologous recombination in embryonic stem cells, we have a ssessed the function of the last gene of the complex, Hoxd-13. Mutant mice displayed skeletal alterations along all body axes suggesting the existence of a general multiaxial patterning system. In limbs, abnorm alities such as a reduction in the length of some bony elements, loss of phalanges, bone fusions, and the presence of an extra element were observed. We propose that the mutation induces local heterochrony, as illustrated by an important retardation in limb-morphogenesis. The rel evance of these observations to our understanding of the development a nd evolution of the tetrapod limb is discussed.