The goal of the experiments in this proposal is to gain a better understanding of the cell biology of cell signaling in development taking advantage of a pleiotropic mutation of Drosophila melanogaster. The product of the shibire gene is required for neural function as well as for normal embryonic development. Mild heat pulses to temperature- sensitive shibire mutants cause paralysis, failure of endocytosis and a failure in cell signaling among cells of developing tissues. One consequence of the failure in cell signaling is a neurogenic phenotype in which the central and peripheral nervous systems are expanded at the expense of the epidermis. Longer heat pulses are tumorigenic, resulting in growth of undifferentiated masses that become transplantable tumors. The shibire product is strikingly similar to the vertebrate protein, dynamin, whose gene has been cloned from mammals including humans. Dynamin is described as a mechanical enzyme that binds to microtubules in a GTP dependent manner. Experiments and longer term projects are proposed which will use genetics and molecular biology to study the cellular functions of potential alternative protein forms of the shibire and their relationship to endocytosis and to cell signaling in development.
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