DEVELOPMENTAL REGULATION OF GROWTH, SIZE AND SHAPE

DESCRIPTION (appended verbatim from investigator's abstract): Size, shape and growth of organisms are determined by the number and size of cells in constituent organs. Cell number is determined as the balance of cell proliferation and cell death (apoptosis). Defects in proliferative control are central to malignancy. Apoptosis is a central feature of heart attack, stroke, and degenerative diseases. There is substantial molecular understanding of intracellular cell cycle and death programs. In vivo regulation must be achieved through extracellular signals which are little understood. Such regulation is probably absent from normal and transformed cells in culture, but can be studied in vivo using the fruitfly Drosophila melanogaster as a model system. In the fruitfly, imaginal disc size is maintained by a homeostatic mechanism called cell competition. Excessive growth on the part of some cells is compensated for by reduced growth and loss of other nearby cells. Deficient growth by some cells always leads to enhanced growth by their neighbors. The molecular and cellular basis of cell competition is unknown. A genetic screen has been developed to identify genes required for cell competition. The role of such genes in growth and homeostasis will be defined through studies of cell proliferation, cell survival and cell size, in part using a new reagent specific for the apoptotic pathway. The molecular identity and role of particular genes in cell competition will be determined. These studies will provide the first genetic and molecular understanding of cell competition. These studies will contribute to basic understanding of the spatial control of growth in vivo and identify genes and pathways that may be important in the cause, prevention , or treatment of heart attack, stroke, cancer, and degenerative diseases.