During development groups of cells must pattern themselves into defined structures. The Drosophila segment and imaginal disc offer particularly advantageous systems in which to study this process. Many of the genes that are involved in patterning these structures have been identified and characterized. By using a combination of genetic and molecular techniques, sophisticated questions can be asked about the function of specific genes and their protein products. The hedgehog (hh) signal transduction pathway plays a central role in the patterning of both segments and imaginal discs. The primary target of Hh signaling appears to be the Cubitus interruptus (Ci) protein. This zinc finger protein regulates the expression of other genes involved in patterning, such as wingless, patched and decapentaplegic. In order to characterize the hh signal transduction pathway and the role of the ci gene in patterning Drosophila, three lines of experiments will be pursued. In the first, clonal analysis with a ci minigene will be used to assay the function of ci in imaginal disc development and to perform epistasis analysis with other genes in this pathway. The second is to study the expression of putative Ci target genes and examine how regulation by Ci is integrated with regulation by other factors. The third approach will use the expression of truncated versions of the Ci protein to carry out a structure-function analysis. These studies will focus on the regulation of the Ci protein and the activation of target genes. By studying the hh signal transduction pathway and the function of the ci gene, the work will contribute significantly to our understanding of basic developmental mechanisms. In addition, amplification of one human homologue of ci, GLI, is associated with certain gliomas and childhood sarcomas and mutations in a second homologue, GLI3, is responsible for Grieg cephalopolysyndactylous syndrome. By understanding the Ci protein in detail, it should be possible to provide insights into the functions of the human homologues.
| Hepker, J; Blackman, R K; Holmgren, R (1999) Cubitus interruptus is necessary but not sufficient for direct activation of a wing-specific decapentaplegic enhancer. Development 126:3669-77 |
