| Important developmental regulatory genes have been conserved from Drosophila to vertebrates. Using this fact as a guide, I sought to identify vertebrate homologues of Drosophila dachshund, a novel nuclear protein critical for normal development of both the eyes and legs. In the process of identifying vertebrate dachshund genes, I identified a dachshund homologue in the butterfly Precis coenia. Expression studies in P. coenia reveal that dachshund is likely to have a conserved role in leg development.;I have also identified two vertebrate homologues of dachshund , Dach1 and Dach2. Characterization and functional studies of these two genes are presented. Dach2 is expressed in the developing somite, in a pattern similar to Pax3 , a gene which is known to induce muscle differentiation. A positive feedback loop exists between Pax3 and Dach2, analogous to a feedback loop that exists in Drosophila between the Pax gene eyeless (a Pax6 homologue) and the dachshund gene. Dach2 can synergistically regulate myogenesis with Eya2 (a vertebrate homologue of the Drosophila gene eyes absent). Moreover, Eya2 can also synergize with Six1 (a vertebrate homologue of the Drosophila gene sine oculis) to regulate myogenesis. The synergistic regulation of muscle development by Dach2 with Eya2 and Eya2 with Six1 parallels the synergistic regulation of Drosophila eye formation by dachshund with eyes absent and eyes absent with sine oculis. This synergistic regulation can be explained at the molecular level by direct physical interactions between Dach2 and Eya2, and Eya2 and Six 1 proteins, which is analogous to interactions observed between the Drosophila proteins. Thus, the Pax, Dach, Eya, and Six genetic network has been conserved across species, but used in a novel developmental context, and expanded to include gene family members which are not directly homologous, for example Pax3 instead of Pax6.;The second vertebrate homologue of dachshund, Dach1 is expressed during limb and neural development. Domains of Dach1 expression overlap with domains of both Pax6 and Pax2 expression, in the developing eye and ear, respectively. Genetic studies in mouse indicate that Dach1 may be operating with different Pax genes in different contexts, though Dach1 is not directly regulated by Pax genes. |
