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PMID: 19164707 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Axon regeneration requires a conserved MAP kinase pathway.

Science (New York, N.Y.) ·Vol. 323 ·No. 5915 ·2009-02-06 ·Pages 802-6

Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani M

Abstract

Regeneration of injured neurons can restore function, but most neurons regenerate poorly or not at all. The failure to regenerate in some cases is due to a lack of activation of cell-intrinsic regeneration pathways. These pathways might be targeted for the development of therapies that can restore neuron function after injury or disease. Here, we show that the DLK-1 mitogen-activated protein (MAP) kinase pathway is essential for regeneration in Caenorhabditis elegans motor neurons. Loss of this pathway eliminates regeneration, whereas activating it improves regeneration. Further, these proteins also regulate the later step of growth cone migration. We conclude that after axon injury, activation of this MAP kinase cascade is required to switch the mature neuron from an aplastic state to a state capable of growth.

MeSH Terms
Aging Animals Axons/physiology,ultrastructure Axotomy Caenorhabditis elegans/genetics,physiology Caenorhabditis elegans Proteins/genetics,metabolism Growth Cones/physiology MAP Kinase Kinase 4/genetics,metabolism MAP Kinase Kinase Kinases/genetics,metabolism MAP Kinase Signaling System Mitogen-Activated Protein Kinases/genetics,metabolism Models, Biological Motor Neurons/physiology Mutation Nerve Regeneration/physiology RNA Interference gamma-Aminobutyric Acid/metabolism
Chemicals
Caenorhabditis elegans Proteins gamma-Aminobutyric Acid Mitogen-Activated Protein Kinases pmk-3 protein, C elegans DLK-1 protein, C elegans MAP Kinase Kinase Kinases MAP Kinase Kinase 4
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hammarlund Marc
Department of Biology, University of Utah, 257 South 1400 East, Salt Lake City, UT 84112-0840, USA.
Nix Paola
Hauth Linda
Jorgensen Erik M
Bastiani Michael
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1165527
Published
2009-02-06
Epub
2009-00-22
Pages
802-6
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2729122
Subset
IM
Grants
NINDS NIH HHS · R21 NS060275 · United States
NINDS NIH HHS · R21 NS060275-02 · United States
NINDS NIH HHS · 1R21NS060275 · United States
NINDS NIH HHS · NS034307 · United States
External Links
PubMed source DOI: 10.1126/science.1165527 PMC Full Text View journal details
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