Tabin, T.: Genetic Cassettes and the Evolution of Regulatory Networks Patterning the Embryo

As genetic regulatory networks underlying development have been uncovered in a variety of organisms, a recurring theme is that the same sets of genes often act in concert in different developmental pathways in the ontogeny of one organism and in both homologous and non-homologous settings in distantly related organisms. A challenge is to explain how such genetic “cassettes,” have been co-selected. An interesting case is the cassette of Pax, eya, six, and dachshund genes, first described in the context of Drosophila eye development. There is a synergistic regulation of eye formation by eya, so(a six gene)and dac. These genes are linked in their regulation so that each positively affects the expression of the others. Moreover,all these genes participate in a positive feedback loop with the upstream gene eya, a Pax6 homologue. We have found that an analogous regulatory network in vertebrate muscle development involving eya2, six1, dac2, and Pax3. Moreover, other members of these families are co-expressed during development of the vertebrate ear and eye. Several evolutionary issues need to be explored. The co-selection of eya, six and dac genes is likely driven by the fact that their gene products physically interact in a functional complex. Different family members may provide different specificities(and the same genes may also function independently of each other in different settings),but it is easy to imagine that expression of one would favor recruitment of a partner and subsequent linking of their regulation. Harder to explain is the similar epistatic relationship with different Pax genes, since they do not interact physically and the Pax genes in question are actually quite distantly related from one another. Finally not all the genetic interrelationships between these genes in the fly eye and vertebrate myogenic cells are recapitulated in the vertebrate eye and ear, which needs to be explained.