Our long-term goal is to understand the genetic control of morphogenesis at the interface between the cellular and tissue levels. Epithelia are well known for being polarized in the apical basal direction. In addition to this type of polarity, many epithelia are also polarized within the plane of the epithelia. For example, the epithelial cells that line our respiratory tract have apical cilia that beat in a polarized manner. The coordination of this beating is essential for the functioning of the tissue. As a model system to study planar polarity I chose tissue polarity in the Drosophila wing. the wing contains about 30,000 cells, each of which produces a single distally pointing cuticular hair. Our genetic analysis showed that the frizzled signaling/signal transduction pathway regulates hair polarity by controlling the subcellular location for hair morphogenesis. During the next 4 years we plan to continue our genetic analysis of a number of tissue polarity genes that we identified during the previous 4 years. The genes and the relevant cDNAs will be cloned and sequenced to determine the nature of the protein product they encode. The developmental expression pattern of the genes will be studied and its significance probed. Genetic epistasis experiments will be done to place the new genes into the appropriate location in the fz pathway and to obtain insights into the developmental mechanisms involved. We will attempt to develop assays that allow us to determine the relationships between individual members of the in-like group of tissue polarity genes. Included in these experiments are ones where our Drosophila developmental genetic approach will be complemented by biochemical experiments to determine how the cytoplasmic Inturned protein is recruited to the vicinity of the cell membrane. We will also carry out experiments designed to distinguish between models proposed to explain the function of the fz signaling/signal transduction pathway in the development of tissue polarity.
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