Evolution and Development of Vertebrate Hox14 Genes

Benaroya Research Institute At Virginia Mason, Seattle WA

Investigators

Abstract

This research will investigate a paralogous group of hitherto unknown vertebrate Hox genes, Hox14. Genes encoding Hoxa14 and Hoxd14 were recently discovered in the coelacanth and elasmobranchs, respectively, and preliminary data suggest that these genes are biologically functional. The findings raise numerous questions germane to the evolution and development of these genes. Four Specific Aims will be pursued. The first two are to clone and genomically-characterize Hox14 genes from the lamprey and lungfish, respectively. Strategies have been designed to take advantage of the laboratory's expertise in the genomic isolation and characterization of vertebrate Hox genes. The third Aim will examine and compare expression patterns of Hox14 genes in both the skate and the lamprey. Functional experiments will be undertaken in the lamprey in order to assess the direct role of Hox14 in embryological development. The fourth Aim will delineate and examine the developmental role of putative cis regulatory elements in the vicinity of the Hoxa14 and Hoxd14 coding sequences. One such element has been shown to be involved in a clear and consistent phenotype in vivo in three surrogate systems, thus strengthening the rationale for this Aim. The four Specific Aims are independent and not contingent on one another. The overarching goal of this research is to understand the role that Hox14 genes may have played in vertebrate evolution and development. The discovery of Hox14 genes in vertebrates was unexpected and their maintenance in distinct vertebrate lineages that diverged some 400 million years ago suggests that they may have played a key developmental role. The "broad impact" of this research is measured in two ways: (1) through employment of highly interdisciplinary approaches to problem solving, including genomics, evolutionary biology, developmental biology and natural history; and (2) by providing a wealth of research and educational resources and opportunities. The research resources include publicly available gene libraries and other reagents. The training opportunities include traineeships for undergraduates of underrepresented minorities.