In order for a multicellular organism to develop properly, it must successfully coordinate the growth and differentiation of tissues across the entire organism. In cancer, the regulatory interactions between cell division and organismal development break down. In some instances, proliferating cancer cells can commandeer endogenous endocrine signals to promote tumor growth and malignancy. The experiments in this proposal investigate the perturbation of endocrine signaling by both regenerative and tumorous cell division at the initiation of metamorphosis in holometabolous insects. In the fruit fly, Drosophila melanogaster, entry into metamorphosis is promoted by the ecdysteroid hormone 20-hydroxyecdysone. However, this endocrine activation of metamorphosis is delayed if larval tissues continue to undergo additional rounds of cell division. By utilizing: a) the ability to regulate hormone levels in Drosophila by feeding exogenous hormone to larvae and adult flies, b) cell and tissue culture and c) genetic screens, I plan to identify the important genes and molecules that mediate the interaction between dividing cells and the Drosophila endocrine system.
