Axon Regeneration Requires a Conserved MAP Kinase Pathway
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 n...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2009-02, Vol.323 (5915), p.802-806 |
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| creator | Hammarlund, Marc Nix, Paola Hauth, Linda Jorgensen, Erik M Bastiani, Michael |
| description | 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. |
| doi_str_mv | 10.1126/science.1165527 |
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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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1165527</identifier><identifier>PMID: 19164707</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Aging ; Animals ; Axons ; Axons - physiology ; Axons - ultrastructure ; Axotomy ; Biological and medical sciences ; Caenorhabditis elegans ; Caenorhabditis elegans - genetics ; Caenorhabditis elegans - physiology ; Caenorhabditis elegans Proteins - genetics ; Caenorhabditis elegans Proteins - metabolism ; Cellular biology ; Developmental biology ; Fundamental and applied biological sciences. Psychology ; gamma-Aminobutyric Acid - metabolism ; Growth cones ; Growth Cones - physiology ; Kinases ; MAP Kinase Kinase 4 - genetics ; MAP Kinase Kinase 4 - metabolism ; MAP Kinase Kinase Kinases - genetics ; MAP Kinase Kinase Kinases - metabolism ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinases - genetics ; Mitogen-Activated Protein Kinases - metabolism ; Models, Biological ; Motor Neurons - physiology ; Mutation ; Nematodes ; Nerve Regeneration - physiology ; Neurology ; Neurons ; Neuroscience ; Physical trauma ; Pseudopodia ; Regeneration ; RNA Interference ; Shock heating ; Vertebrates: nervous system and sense organs</subject><ispartof>Science (American Association for the Advancement of Science), 2009-02, Vol.323 (5915), p.802-806</ispartof><rights>Copyright 2009 American Association for the Advancement of Science</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-75cb09de9601052ab764e41e797cdd0c5ec8fbe8d4e9eb1eb38ba48451c9acd83</citedby><cites>FETCH-LOGICAL-c653t-75cb09de9601052ab764e41e797cdd0c5ec8fbe8d4e9eb1eb38ba48451c9acd83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20403030$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20403030$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21123949$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19164707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hammarlund, Marc</creatorcontrib><creatorcontrib>Nix, Paola</creatorcontrib><creatorcontrib>Hauth, Linda</creatorcontrib><creatorcontrib>Jorgensen, Erik M</creatorcontrib><creatorcontrib>Bastiani, Michael</creatorcontrib><title>Axon Regeneration Requires a Conserved MAP Kinase Pathway</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>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.</description><subject>Aging</subject><subject>Animals</subject><subject>Axons</subject><subject>Axons - physiology</subject><subject>Axons - ultrastructure</subject><subject>Axotomy</subject><subject>Biological and medical sciences</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans - genetics</subject><subject>Caenorhabditis elegans - physiology</subject><subject>Caenorhabditis elegans Proteins - genetics</subject><subject>Caenorhabditis elegans Proteins - metabolism</subject><subject>Cellular biology</subject><subject>Developmental biology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Growth cones</subject><subject>Growth Cones - physiology</subject><subject>Kinases</subject><subject>MAP Kinase Kinase 4 - genetics</subject><subject>MAP Kinase Kinase 4 - metabolism</subject><subject>MAP Kinase Kinase Kinases - genetics</subject><subject>MAP Kinase Kinase Kinases - metabolism</subject><subject>MAP Kinase Signaling System</subject><subject>Mitogen-Activated Protein Kinases - genetics</subject><subject>Mitogen-Activated Protein Kinases - metabolism</subject><subject>Models, Biological</subject><subject>Motor Neurons - physiology</subject><subject>Mutation</subject><subject>Nematodes</subject><subject>Nerve Regeneration - physiology</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neuroscience</subject><subject>Physical trauma</subject><subject>Pseudopodia</subject><subject>Regeneration</subject><subject>RNA Interference</subject><subject>Shock heating</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAUhS0EosPAmhUQIQGr0Ot3vKk0GvESRVRA15bj3EwzmnFaO-nj3-NhohZYgLywrs7nc-VzCHlK4S2lTB0m32HwmAclJdP3yIyCkaVhwO-TGQBXZQVaHpBHKa0Bsmb4Q3JADVVCg54Rs7juQ_ENVxgwuqH7NVyMXcRUuGLZh4TxEpviy-Kk-NwFl7A4ccPZlbt5TB60bpPwyXTPyen7dz-WH8vjrx8-LRfHpVeSD6WWvgbToFFAQTJXayVQUNRG-6YBL9FXbY1VI9BgTbHmVe1EJST1xvmm4nNytPc9H-stNh7DEN3Gnsdu6-KN7V1n_1RCd2ZX_aVlmhnKWDZ4MxnE_mLENNhtlzxuNi5gPyarBZdaSrEjX_-TVKoyQmb-f2COn0taQQZf_gWu-zGGnJdllOdIlN6tPdxDPvYpRWxvP0fB7mq2U812qjm_eP57Jnf81GsGXk2AS95t2uiC79Itx7IrN8Jk7tmeW6ehj3c6COC7Mycv9nrreutWMXucfmdAOVBpAKjmPwGqHcOe</recordid><startdate>20090206</startdate><enddate>20090206</enddate><creator>Hammarlund, Marc</creator><creator>Nix, Paola</creator><creator>Hauth, Linda</creator><creator>Jorgensen, Erik M</creator><creator>Bastiani, Michael</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090206</creationdate><title>Axon Regeneration Requires a Conserved MAP Kinase Pathway</title><author>Hammarlund, Marc ; Nix, Paola ; Hauth, Linda ; Jorgensen, Erik M ; Bastiani, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653t-75cb09de9601052ab764e41e797cdd0c5ec8fbe8d4e9eb1eb38ba48451c9acd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aging</topic><topic>Animals</topic><topic>Axons</topic><topic>Axons - physiology</topic><topic>Axons - ultrastructure</topic><topic>Axotomy</topic><topic>Biological and medical sciences</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans - genetics</topic><topic>Caenorhabditis elegans - physiology</topic><topic>Caenorhabditis elegans Proteins - genetics</topic><topic>Caenorhabditis elegans Proteins - metabolism</topic><topic>Cellular biology</topic><topic>Developmental biology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Growth cones</topic><topic>Growth Cones - physiology</topic><topic>Kinases</topic><topic>MAP Kinase Kinase 4 - genetics</topic><topic>MAP Kinase Kinase 4 - metabolism</topic><topic>MAP Kinase Kinase Kinases - genetics</topic><topic>MAP Kinase Kinase Kinases - metabolism</topic><topic>MAP Kinase Signaling System</topic><topic>Mitogen-Activated Protein Kinases - genetics</topic><topic>Mitogen-Activated Protein Kinases - metabolism</topic><topic>Models, Biological</topic><topic>Motor Neurons - physiology</topic><topic>Mutation</topic><topic>Nematodes</topic><topic>Nerve Regeneration - physiology</topic><topic>Neurology</topic><topic>Neurons</topic><topic>Neuroscience</topic><topic>Physical trauma</topic><topic>Pseudopodia</topic><topic>Regeneration</topic><topic>RNA Interference</topic><topic>Shock heating</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hammarlund, Marc</creatorcontrib><creatorcontrib>Nix, Paola</creatorcontrib><creatorcontrib>Hauth, Linda</creatorcontrib><creatorcontrib>Jorgensen, Erik M</creatorcontrib><creatorcontrib>Bastiani, Michael</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Ecology Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hammarlund, Marc</au><au>Nix, Paola</au><au>Hauth, Linda</au><au>Jorgensen, Erik M</au><au>Bastiani, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Axon Regeneration Requires a Conserved MAP Kinase Pathway</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2009-02-06</date><risdate>2009</risdate><volume>323</volume><issue>5915</issue><spage>802</spage><epage>806</epage><pages>802-806</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Regeneration of injured neurons can restore function, but most neurons regenerate poorly or not at all. 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| ispartof | Science (American Association for the Advancement of Science), 2009-02, Vol.323 (5915), p.802-806 |
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| subjects | Aging Animals Axons Axons - physiology Axons - ultrastructure Axotomy Biological and medical sciences Caenorhabditis elegans Caenorhabditis elegans - genetics Caenorhabditis elegans - physiology Caenorhabditis elegans Proteins - genetics Caenorhabditis elegans Proteins - metabolism Cellular biology Developmental biology Fundamental and applied biological sciences. Psychology gamma-Aminobutyric Acid - metabolism Growth cones Growth Cones - physiology Kinases MAP Kinase Kinase 4 - genetics MAP Kinase Kinase 4 - metabolism MAP Kinase Kinase Kinases - genetics MAP Kinase Kinase Kinases - metabolism MAP Kinase Signaling System Mitogen-Activated Protein Kinases - genetics Mitogen-Activated Protein Kinases - metabolism Models, Biological Motor Neurons - physiology Mutation Nematodes Nerve Regeneration - physiology Neurology Neurons Neuroscience Physical trauma Pseudopodia Regeneration RNA Interference Shock heating Vertebrates: nervous system and sense organs |
| title | Axon Regeneration Requires a Conserved MAP Kinase Pathway |
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