GSBS Dissertations and Theses

ORCID ID

0000-0002-0179-2973

Publication Date

2019-11-25

Document Type

Doctoral Dissertation

Academic Program

Interdisciplinary Graduate Program

Department

Neurobiology

First Thesis Advisor

Alexandra Byrne

Keywords

C. elegans, functional axon regeneration, axon regeneration, PARP, calpain, IMPDH

Abstract

How do organisms attain the capacity to regenerate a structure, entire body, or not to regenerate? These are fundamental questions in biology for understanding how replicative systems are evolved to renew, age, and/or die. One outstanding question in regenerative biology that attracts attention is how and why the human central nervous system fails to regenerate after injury. Nervous system injuries are characterized by axonal damage and loss of synaptic function that contribute to debilitating neuronal dysfunctions. Although the molecular underpinnings of axon regeneration are well characterized, very little is known about how and what molecular pathways modulate reformation of synapses within regenerating axons to restore function. Thus, understanding the fundamental molecular and genetic mechanisms of functional axon regeneration (FAR), restoration of both axon and synapse, for the functional recovery of the nervous system remains elusive.

In Chapter I, I outline the biology of regeneration and provide evolutionary perspectives of this phenomenon. Then, I provide clinical perspectives of central nervous system regeneration and therapeutic innovations. I next introduce the regulators of axon regeneration and how C. elegans as a genetic system allows detailed characterization of axon regeneration. In Chapter II, using C. elegans as a platform, I show how axon regeneration and synaptic reformation are controlled by distinct genetic pathways. I show how Poly-ADP ribose polymerase (PARP) pathway modulates functional restoration by regulating divergent genetic pathways leading to axon regeneration and synapse restoration. Finally, in Chapter III, I summarize the model of axon regeneration, evolutionary perspectives, and epistemic limitations of C. elegans axon regeneration.

DOI

10.13028/atj3-yz16

Rights and Permissions

Copyright is held by the author, with all rights reserved.

Available for download on Thursday, December 23, 2021

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