Pax6 and the genetic regulation of eye development in Tribolium

Wayne State University, Detroit MI

Investigators

Abstract

Pax6 genes encode a highly conserved DNA binding protein (transcription factor), which performs essential regulatory functions during eye development in most animal species investigated including humans. How Pax6 adopted and executes this deeply conserved role is not yet completely understood. One question is whether Pax6 acts by specifying a large region of the head, where the eyes will develop, or by more specifically instructing the cells that will differentiate into retina. Another question is whether Pax6 acts solely at the top or at multiple levels of the network of genetic interactions, which orchestrate the development of the eye. This project will elucidate how Pax6 regulates eye development in insects by determining the consequences of downregulating Pax6 expression in the developing eye of the flour beetle Tribolium castaneum. Preliminary data indicate significant differences to the fruit fly Drosophila melanogaster, where Pax6 has likewise been extensively studied. The strategy employed in this project takes advantage of the genome sequence information available in both species, which allows for efficient determination of gene expression levels by high throughput sequencing. Moreover, the comparison between Tribolium and Drosophila will reveal mechanisms that have remained conserved since the separation of the two species at least 300 million years ago and can therefore be assumed to be of universal importance in animal eye development. Tribolium and related darkling beetles (Tenebrionidae) are pest species of major economic impact. In addition, mutations of Pax6 in humans are associated with severe visual birth defects. Therefore, results from this research will benefit ongoing efforts to solve food storage and human health problems. This research will also enhance the professional training of one Ph.D. student and a postdoctoral research assistant as well as education in the USA as experimental modules of the project will be integrated in a laboratory class offered to undergraduate and graduate students.