CAREER: Mechanisms of Intercellular Communication in Drosophila

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The secreted signaling molecule, Wingless (Wg) and its vertebrate homologues, the Wnt family, play critical roles in generating embryonic positional information and in regulating cell proliferation. Recent work in this laboratory has revealed that active cellular transport of the Wingless signaling molecule is essential for specification of cell fates in the embryonic epidermis of Drosophila. A mutant form of Wg that shows restricted movement away from the cells that produce it is associated with a reduction in the diversity of cell fates normally specified by Wg signaling. Thus, lateral movement of Wg through cells in the epidermal epithelium is functionally important for cell fate specification. This planar form of transcytosis is very different from known instances of transcytosis, which occur in an apical-basal or basal-apical direction across a polarized epithelium. Understanding the mechanism of this novel intercellular transport is essential to the study of Wg/Wnt biology. The specific goals of this proposal seek to: (1) identify structural features of the Wg protein, and of Wnt proteins in general, that are required for transport; (2) explore the cellular machinery responsible for effecting the movement of Wg by perturbing the endocytic process both in vivo and in vitro; and (3) characterize genetically and molecularly two new genes that appear to be involved in Wg protein transport during development. This research work has inspired the development of demonstration materials for stimulating interest in biology in pre-college, undergraduate and graduate educational settings. Drosophila mutant strains are commonly used for demonstrating genetic principles, but they can also provide dramatic illustrations of basic developmental and cell biological phenomena such as pattern formation and endocytosis. A major goal of the proposed education plan is to develop and popularize their use for these purposes in the classroom. Specific goals include improving several fly strains for easier manipulation by educators, writing a set of instructional materials to present and explain the cellular phenomena at increasing levels of sophistication, and piloting the use of these demonstration materials in an advanced undergraduate cell biology course at Northwestern University.