COLLAZO, Andres; BRICAUD, Olivier; ZELLER, Robert W.; House Ear Institute, Los Angeles; House Ear Institute, Los Angeles; San Diego State University: Developmental role of the Pax-Six-Eya-Dach gene regulatory network during chordate evolution

Many studies in Drosophila have demonstrated that members of the Pax, Six, Eya and Dach gene families interact with each other and are critical for early eye development. In vertebrates, members of the Pax-Six-Eya-Dach regulatory network are necessary for the development of such organs and tissues as the inner ear, eye, kidney and muscle. The vertebrate inner ear functions in balance and hearing, the former being an ancient sensory modality for metazoans. The major role of this network in inner ear development is to regulate cell proliferation and death, which is critical for the normal patterning and growth of this structure. In our studies of the teleost, Danio rerio, we found that loss and gain of function of a member of this network, six1, results in a weaker and in some cases quite different phenotype than found in the mouse Six1 loss of function studies. This difference may be due to the gene duplications found in the lineage leading to teleost as compared to amniotes such as mammals. The function of Six1 and other members of the Pax-Six-Eya-Dach regulatory network may not be different but spatio-temporal differences in the co-expression of these genes in these two vertebrates could explain the conflicting results. To determine which role is ancestral for chordates we will look at an outgroup, the ascidian Ciona intestinalis, whose genome has been sequenced and contains homologues of all four gene families. Ciona provides a powerful system for gene function assays and has homologues for all the organs and tissues to be studied. It will be interesting to determine if the role of this pathway in sensory structures is ancestral, as it may be in metazoans, while the role in muscle and kidney is an evolutionarily later cooption.