Title

Cell Biology of Axon Degeneration and Regeneration In Vivo

Date of Award

Fall 10-1-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

First Advisor

Hammarlund, Marc

Abstract

Axons are fundamental connective units that mediate information flow in nervous systems. Axon degeneration breaks neural circuits and is a hallmark of neurodegenerative diseases. Axon regeneration has the potential to repair damaged circuits. Here I investigate the molecular and cellular mechanisms underlying both axon degeneration and regeneration in C. elegans in vivo. In the first part of the dissertation, I examine a specific type of axon degeneration that is caused by mitochondria defects. I describe a novel calsyntenin-CaMKII-Sarm1-MAPK pathway involved in this type of axon degeneration. I further demonstrate that by modulating this signaling pathway, degeneration can be dramatically delayed. The second part of this dissertation focuses on a critical yet overlooked step of axon regeneration that is essential for circuit rewiring – synapse regeneration. Using the novel DA9 regeneration model, I identify two key choke points that limit synaptic reformation and functional recovery: one is the deficient molecular composition of new presynapses and the other is breakdown of synaptic polarity. Overall, my work reveals mechanisms underpinning axon degeneration and regeneration and opens up new areas for developing treatments to promote axon health.

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