Coordination of growth and patterning during development

Columbia University Health Sciences, New York NY

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Abstract

DESCRIPTION (provided by applicant): The overall goal of this proposal is to understand the molecular mechanisms that link cell growth, cell division, and cell fate patterning during development. Animal growth results from the precise coordination of these different processes, as well as from complex interactions between neighboring cells within individual organs and tissues. Although the molecular pathways that control cell proliferation, cellular biosynthesis, and cell fate specification are known, what remains unclear is how they intersect and are influenced by each other during the development of tissues and organs. To this end, we propose in vivo studies to determine the mechanisms that link growth to pattern formation, using the Drosophila wing as a model system. This proposal has three major goals. First, we will determine how Wingless, a member of the conserved Wnt gene family of pattern regulators, directs growth of the developing wing. These studies will identify the growth regulatory targets and mechanisms used by Wingless to control cellular growth, cell cycle progression, and cell survival in vivo. Second, we will use a series of genetic and molecular assays to understand the intrinsic genetic program that regulates organ size. Our experiments will address how developing organs monitor their mass, how cells sense growth rate differences between themselves, which growth parameters respond to growth alterations, and determine how these features interact to control wing size and shape. Third, to determine the connections between growth and patterning we will carry out a genetic screen to identify genes that promote cell autonomous growth without altering pattern. Drosophila has been a pioneering genetic model system for many years, and our studies provide an opportunity for a powerful analysis of the fundamental molecular linkages underlying cell, organ, and animal growth. These studies are germane to an understanding of growth during human development, and as such, may lead to new therapies to promote tissue regeneration and transplantation, a well as those to prevent diseases of pathological growth such as cancer.