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    The Roles of daf-6 and Cell-Cell Interactions in Sensory Organ Morphogenesis

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    The development of multicellular organs depends on the regulation of cell shape, position, and orientation. The genetic regulation of these morphogenetic processes is poorly understood. As a model for organ morphogenesis, I studied the development of the Caenorhabditis elegans amphid sensory organ. Sensory organs in diverse species are often composed of neuronal sensory endings accommodated in a lumen formed by ensheathing epithelia or glia. The generation of this structure may require cell-autonomous factors that control lumen formation, as well as cell non-autonomous factors that coordinate the morphogenesis of the lumen with the resident neuronal processes. Understanding these processes would provide insight into lumen formation, glia morphogenesis, and cell-cell interactions during development, especially neuronal regulation of glia morphogenesis. In this thesis, I identify and characterize genes required for lumen formation in the amphid sensory organ. First, the gene daf-6 is required cell autonomously during amphid lumen formation. daf-6 encodes a Patched-related protein that is a member of a previously uncharacterized sub-family of sterolsensing domain containing proteins. Interestingly, daf-6 is expressed and required in several tubular structures, such as the excretory system and vulva. Thus, a similar genetic pathway is required for the formation of different lumens. Secondly, I conducted a forward genetic screen and identified and characterized mutations that suppress the lumen formation defects in daf-6 mutants. Finally, by examining mutants defective in sensory neuron process formation, I showed that amphid lumen shape is determined by its resident sensory endings