The overall objective of these studies is to understand the biochemical mechanisms used to generate and transmit information for dorsal-ventral asymmetry in the Drosophila egg and embryo. The position of a cell along the dorsal-ventral axis defines its developmental fate, determining whether the cell will become part of the muscle, the nervous system, or the ventral or dorsal epidermis. Embryonic polarity is established by a group of maternal effect genes that encode the components of a signal transduction pathway. The primary focus will be on understanding the action of the extracellular signaling molecule encoded by the spatzle gene. Genetic and molecular biological experiments suggest that the spatzle protein is activated on the ventral side of the embryo by the protease encoded by easter; this processed spatzle protein then determines where the receptor Toll is active, possibly by acting as a receptor ligand. The proposed experiments will use purified proteins to biochemically address this model, in order to determine: (1) whether the precursor spatzle protein is cleaved by the easter protein; (2) how processing leads to a biologically active form of the spatzle protein; and (3) whether purified processed spatzle protein binds directly to Toll, or to another effector molecule. Reagents will be synthesized to detect the processed form in the embryo, and to visualize the gradient of positional information. A genetic screen has identified other loci involved in the dorsal-ventral pathway. A genetic and molecular characterization will be carried out on one of these genes, fettucine, which apparently acts during oogenesis to help localize the initial asymmetric determinant. Defining the molecular mechanisms establishing embryonic polarity will broaden our understanding of signaling reactions in other developmental pathways.
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