GENETIC CONTROL OF MICROTUBULE FUNCTION IN DEVELOPMENT

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The overall question which this research addresses is how the information encoded in linear form in the genome is utilized to achieve functional three-dimensional cellular substructure. The proposed research utilizes a molecular and genetic analysis of microtubule function in Drosophila. Microtubules are ubiquitous eukaryotic organelles required for many cellular processes, including cell division, mediation of cell shape, and motility of cilia and flagella. The basic unit in microtubule assembly is the alpha, beta tubulin heterodimer. Higher eukaryotes express multiple tubulin isoforms which are distinct but related proteins encoded in small multi-gene families. In addition, other proteins, collectively termed microtubule-associated proteins, are required for specific microtubule arrays. Thus, each microtubule-based structure is unique in architecture, mode of function, and total spectrum of constitutent proteins. This research addresses the nature of the genetic controls which govern how cells utilize one organelle, the microtubule, to form many morphologically and functionally distinct structures. The proposed experiments constitute genetic, biochemical, and molecular analysis of the function of Drosophila beta-tubulins during development, in differentiation of adult tissues, and in gametogenesis. The specific goals are: [1]Definition of the relationship between beta-tubulin structure and function using genetic analysis of multiple microtubule functions in the male germ line as a model system. Specific beta tubulin mutations and hybrid beta tubulin genes will be constructed and introduced into the genome in order to examine the function of particular beta tubulin domains and to test the hypothesis that divergent beta-tubulin isoforms have restricted or specialized properties. [2]Genetic, molecular, and developmental analysis of two divergent developmentally-regulated beta tubulin isoforms, beta3-tubulin and beta4-tubulin, to determine their specific roles in each of the cell types in which they are expressed.