A DLK And JNK Dependent Axon Self-Destruction Program Promotes Wallerian Degeneration

Axon loss is a debilitating consequence of a wide range of neurological conditions. As axons degenerate, they go through a stereotyped sequence of morphological changes termed Wallerian degeneration. It has long been hypothesized that there is an active axonal breakdown program, conceptually similar to apoptosis, which underlies Wallerian degeneration. However, the molecular pathways that accomplish this program in neurons have remained elusive. We demonstrate that dual leucine kinase: DLK) promotes degeneration of severed axons in Drosophila and mice, and its target JNK promotes degeneration locally in axons as they commit to degenerate. This pathway also promotes degeneration after chemotherapy exposure, and thus may be a component of a general axon self-destruction program.

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biology and Biomedical Sciences: Neurosciences

Year dc:date.available

2011

Author dc:creator

• Miller, Bradley

Contributors dc:contributor

• Aaron DiAntonio

• Neurosciences
• Axon Degeneration
• DLK
• JNK

Language dc:language

English (en)

DOI

https://doi.org/10.7936/K79K4889

OAI identifier oai:identifier

oai:openscholarship.wustl.edu:etd-1871