The control of the final size of an organ and an organism is a fundamental problem in developmental biology. In the last few years, some answers have begun to emerge from Drosophila melanogaster, with the identification of some regulators of cell and tissue growth, Loss-of-function mutations, for the dmyc and cdk4 genes and for genes encoding some components of the insulin-like growth factor pathway (chico, inr, dS6K), produce small flies. In order to identify new regulators of cell and tissue growth, I propose to re-evaluate existing mutants that affect animal size. I will use genetic and genomic information and modern methods of analysis to understand the growth abnormalities in these mutants which were isolated in 30's and 50's by Bridges and Morgan, and Fahmy. A number of these mutants have been lost, suggesting that there may be many more genes to be identified. I will perform a genetic screen on the X chromosome for modifications of the size of a clonal wing compartment. The analysis of these mutants will follow this program: First, I will test if these mutations affect cell or tissue growth and cell cycle progression by clonal analysis in adult appendages and by flow cytometric (FACS) analysis. Second, genes which show interesting phenotypes will be characterized by genetic mapping, molecular cloning and rescue. Third, to confirm their role in the regulation of growth and cell proliferation, I will test if over-expression gives an opposite phenotype to loss of function. Finally, I will examine genetic interactions with pathways known to be involved in the coordination of growth and cell proliferation.