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

Abstract

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.