Student Theses and Dissertations

Taulant Bacaj

Date of Award

2009

Document Type

Thesis

RU Laboratory

Shaham Laboratory

Keywords

nervous system development, C. elegans, sensory organs, glia, sensory cilia

Abstract

The nervous system emerges from the coordinated development of neurons and glia. To better understand the processes that enable nervous system development and function we have studied the sensory organs of Caenorhabditis elegans because their anatomy and function are well-characterized. Specifically, we have focused on two aspects of sensory organs: how do glia interact with neurons to enable proper development and function and how are sensory cilia generated. To uncover any glial roles, we ablated the major glial cell of the amphid sensilla. Embryonic glial ablation did not affect neuronal survival and resulted in sensory neuron dendrites that were far too short, revealing a glial role in anchoring sensory neuron dendrites. To examine post-developmental glial roles, we ablated glia after the amphid sensory organ was fully formed. These glia-ablated animals exhibited profound sensory deficits as determined by behavioral assays, failed to maintain the proper morphology of some modified sensory cilia, and had defects in neuronal uptake of lipophilic dyes. Further, animals lacking glia showed no Ca2+ responses in the ASH sensory neuron after stimulation with a high osmolarity solution. To understand the molecular bases of these glial activities, we characterized a sheath glia expressed gene, fig-1, that encodes a protein with thrombospondin type I domains. FIG-1 likely functions extracellularly, is essential for neuronal dye uptake, and also affects behavior. To characterize the molecular basis of cilia morphogenesis and function, we cloned the che-12 and dyf-11 mutants which have chemotaxis and dye uptake defects. CHE-12 and DYF-11 are conserved ciliary proteins required for maintenance of cilium morphology and function. Furthermore, DYF-11 undergoes intraflagellar transport (IFT) and may function at an early stage of IFT-B particle assembly. Our results suggest that glia are required for multiple aspects of sensory organ function. Moreover, as thrombospondin 1 is a glial-secreted protein required for synapse formation in mice, these results suggest that some of the molecular components underlying glia-neuron interactions in C. elegans might be conserved.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/409

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