Student Theses and Dissertations

Date of Award

2011

Document Type

Thesis

RU Laboratory

Shaham Laboratory

Abstract

Sensory organs are the gates through which information flows into the nervous system. In most animals, such organs consist of sensory neurons, which can transform stimuli into changes in their membrane potential, and glial cells, which establish a niche important for the morphogenesis and function of the neurons. Although similar glial compartments are seen throughout the nervous system, their morphogenesis is poorly understood. In the work presented here, I use the main sensory organ of Caenorhabditis elegans, the amphid, as a model system for understanding how glia form these compartments. First, by the interpretation of electron microscopy reconstructions of the developing amphid, I was able to uncover a role for daf-6/Patched, an established regulator of amphid morphogenesis, in restricting the size of the sensory compartment. Second, I sought to identify genes acting in the opposite direction, in expanding the sensory compartment, by cloning and characterizing suppressors of daf-6. Through this approach I discovered that lit-1/Nlk acts within glia, in counterbalance to daf-6, to promote sensory compartment expansion. Although LIT-1 has been shown to regulate Wnt signaling, my genetic studies demonstrate a novel, Wnt-independent role for LIT-1 in sensory compartment size control. The LIT-1 activator MOM-4/TAK1 is also important for compartment morphogenesis and both proteins line the glial sensory compartment. LIT-1 compartment localization is important for its function and requires neuronal signals. Furthermore, the conserved LIT-1 C-terminus is necessary and sufficient for this localization. Two-hybrid and co-immunoprecipitation studies demonstrate that the LIT-1 C-terminus binds both actin and the Wiskott-Aldrich syndrome protein (WASP), an actin regulator. I show that actin also lines the sensory compartment, and that WASP is important for compartment expansion, potentially by functioning in the same pathway as LIT-1. These results suggest that the daf-6 and lit-1 glial pathways constitute a rheostat used to control sensory compartment size. Finally, I also identify a role for the retromer complex, a module involved in the recycling of transmembrane proteins and membrane material from the endosomes to the Golgi apparatus, in amphid morphogenesis. Similar to lit-1, mutations of retromer components suppress daf-6, suggesting that the retromer could also act in promoting sensory compartment expansion.

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/10209/507

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