Developmental control of tissue growth in Drosophila by proliferation and apoptosis pathways.
Research Goals Our work uses the fruit fly Drosophila melanogaster to address the important biological question of how signaling pathways limit cell number and cell growth during metazoan development. Metazoan development involves huge increases in cell number and total cell mass that must be coordinated through time and space to achieve the adult form. Study of these pathways is therefore fundamental to the study of developmental patterning mechanisms, and also relates directly to the cell biological consequences of genetic lesions that underlie hyperplastic phenotypes like cancer. Current research The lab is currently focused on studying three genes that inhibit overgrowth in the developing fly eye: archipelago, erupted, and gang of four. archipelago and gang of four each function cell autonomously to restrict cell proliferation, while erupted encodes a potent inhibitor of tissue growth that functions non-cell autonomously. We have cloned archipelago and erupted, and the mapping of gang of four is underway. Our work shows that archipelago inhibits growth by degrading protein targets that include Cyclin E and dMyc, the fly ortholog of the human c-Myc cancer oncogene. Human archipelago is functionally conserved and is mutated in a variety of human cancers. Identification of the erupted gene reveals that it also may shed light on mechanisms of carcinogenesis in mammals. erupted encodes a sequence homolog of an enigmatic human gene with proposed tumor suppressor activity. Analysis of the function and regulation of archipelago and erupted using both genetic and biochemical techniques are ongoing.
