Axon Degeneration in C. Elegans

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Publication Type dissertation
School or College School of Medicine
Department Neurology
Author Rawson, Randi L.
Title Axon Degeneration in C. Elegans
Date 2014-08
Description Axons degenerate following injury and during "dying-back" neurodegenerative diseases, which are characterized by early degeneration of synapses and axons. While injury and disease are clearly distinct events, they share some common regulators. Although these problems have been extensively studied, very little is known about which molecules initiate and execute the degeneration process. Uncovering mediators of axonal degeneration could provide new therapeutic targets for the treatment of neurodegenerative disease. This dissertation studies axon degeneration in the nematode Caenorhabditis elegans, where degeneration can be induced genetically or by injury. Axons degenerate in a manner consistent with Wallerian degeneration; they swell and fragment into debris particles that are engulfed by other cells. I have studied two main aspects of axon degeneration. First, I have shown that mitochondria are required to prevent the initiation of axon degeneration. I characterize a novel gene ric-7, which is required for mitochondrial export from neuronal cell bodies. In both ric-7 mutant and wild-type axons, degeneration is enhanced in the absence of mitochondria. Thus, mitochondria primarily protect axons and are not required for the execution of degeneration. Second, I have identified genes required for nonprofessional phagocytes to engulf neuronal debris following degeneration. I demonstrate that hypodermal cells engulf degenerating axons in C. elegans and that only some of the programmed cell death (ced) genes are involved. There are two parallel pathways that mediate engulfment of cell corpses during apoptosis; ced-1, -6, -7 and ced-2, -5, -10, -12. Both ced-1 and ced-6 are required for engulfment of degenerating axons, but not the parallel ced-2, -5, -12 pathway. Thus, epithelial cells engulf degenerating axons in a manner that is distinct from both apoptosis and macrophage/gliamediated engulfment of degenerating axons. C. elegans will be a useful model system for uncovering novel regulators of mitochondria-mediated axon protection and epithelia-mediated engulfment.
Type Text
Publisher University of Utah
Subject MESH Caenorhabditis elegans; Drosophila; Axons; Retrograde Degeneration; Wallerian Degeneration; Neurodegenerative Diseases; Mitochondria; Autophagy; Apoptosis; Oxidative Phosphorylation; Nerve Net; Wallerian Degeneration
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital version of Axon Degeneration in C. Elegans
Rights Management Copyright © Randi L. Rawson 2014
Format Medium application/pdf
Format Extent 31,578,265 bytes
Source Original in Marriott Library Special Collections
ARK ark:/87278/s6bg7255
Setname ir_etd
Date Created 2019-03-11
Date Modified 2021-05-06
ID 1404036
Reference URL