{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:14:43Z","timestamp":1787242483966,"version":"build-2736575974"},"reference-count":61,"publisher":"Society for Neuroscience","issue":"47","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":231,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2019,11,20]]},"abstract":"<jats:p>Regenerating axons often have to grow considerable distances to reestablish circuits, making functional recovery a lengthy process. One solution to this problem would be to co-opt the \u201ctemporal\u201d guidance mechanisms that control the rate of axon growth during development to accelerate the rate at which nerves regenerate in adults. We have previously found that the loss of Limk1, a negative regulator of cofilin, accelerates the rate of spinal commissural axon growth. Here, we use mouse models to show that spinal motor axon outgrowth is similarly promoted by the loss of Limk1, suggesting that temporal guidance mechanisms are widely used during development. Furthermore, we find that the regulation of cofilin activity is an acute response to nerve injury in the peripheral nervous system. Within hours of a sciatic nerve injury, the level of phosphorylated cofilin dramatically increases at the lesion site, in a Limk1-dependent manner. This response may be a major constraint on the rate of peripheral nerve regeneration. Proof-of-principle experiments show that elevating cofilin activity, through the loss of Limk1, results in faster sciatic nerve growth, and improved recovery of some sensory and motor function.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    The studies shed light on an endogenous, shared mechanism that controls the rate at which developing and regenerating axons grow. An understanding of these mechanisms is key for developing therapies to reduce painful recovery times for nerve-injury patients, by accelerating the rate at which damaged nerves reconnect with their synaptic targets.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.0648-19.2019","type":"journal-article","created":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T17:45:11Z","timestamp":1570038311000},"page":"9316-9327","source":"Crossref","is-referenced-by-count":21,"title":["The Cofilin\/Limk1 Pathway Controls the Growth Rate of Both Developing and Regenerating Motor Axons"],"prefix":"10.1523","volume":"39","author":[{"given":"Michele E.","family":"Frendo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Phan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soizic","family":"Riche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2019,10,2]]},"reference":[{"key":"2023041803385021000_39.47.9316.1","doi-asserted-by":"publisher","DOI":"10.1038\/86011"},{"key":"2023041803385021000_39.47.9316.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.038"},{"key":"2023041803385021000_39.47.9316.3","doi-asserted-by":"publisher","DOI":"10.1038\/31729"},{"key":"2023041803385021000_39.47.9316.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80827-2"},{"key":"2023041803385021000_39.47.9316.5","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830111013"},{"key":"2023041803385021000_39.47.9316.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2008.02.002"},{"key":"2023041803385021000_39.47.9316.7","doi-asserted-by":"publisher","DOI":"10.3791\/3606"},{"key":"2023041803385021000_39.47.9316.8","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-6-6"},{"key":"2023041803385021000_39.47.9316.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2006.11.011"},{"key":"2023041803385021000_39.47.9316.10","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3609"},{"key":"2023041803385021000_39.47.9316.11","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01051.2009"},{"key":"2023041803385021000_39.47.9316.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00254-X"},{"key":"2023041803385021000_39.47.9316.13","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02762"},{"key":"2023041803385021000_39.47.9316.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2008.03.018"},{"key":"2023041803385021000_39.47.9316.15","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0812s15"},{"key":"2023041803385021000_39.47.9316.16","doi-asserted-by":"publisher","DOI":"10.1242\/dev.160093"},{"key":"2023041803385021000_39.47.9316.17","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(88)90194-8"},{"key":"2023041803385021000_39.47.9316.18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-07-02527.2003"},{"key":"2023041803385021000_39.47.9316.19","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1120"},{"key":"2023041803385021000_39.47.9316.20","doi-asserted-by":"publisher","DOI":"10.1101\/gr.092114.109"},{"key":"2023041803385021000_39.47.9316.21","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00178-1"},{"key":"2023041803385021000_39.47.9316.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906809106"},{"key":"2023041803385021000_39.47.9316.23","doi-asserted-by":"publisher","DOI":"10.3791\/3564"},{"key":"2023041803385021000_39.47.9316.24","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-110"},{"key":"2023041803385021000_39.47.9316.25","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2836-04.2004"},{"key":"2023041803385021000_39.47.9316.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6156-10.2011"},{"key":"2023041803385021000_39.47.9316.27","doi-asserted-by":"publisher","DOI":"10.1001\/archfaci.7.1.17"},{"key":"2023041803385021000_39.47.9316.28","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"2023041803385021000_39.47.9316.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.06.017"},{"key":"2023041803385021000_39.47.9316.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2005.11.005"},{"key":"2023041803385021000_39.47.9316.31","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.5435\/00124635-201102001-00006","article-title":"Limb salvage with major nerve injury: current management and future directions","volume":"19","author":"Kang","year":"2011","journal-title":"J Am Acad Orthop Surg"},{"key":"2023041803385021000_39.47.9316.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.12.004"},{"key":"2023041803385021000_39.47.9316.33","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050484"},{"key":"2023041803385021000_39.47.9316.34","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90045-0"},{"key":"2023041803385021000_39.47.9316.35","doi-asserted-by":"publisher","DOI":"10.1053\/jhsu.2000.4165"},{"key":"2023041803385021000_39.47.9316.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4550-11.2011"},{"key":"2023041803385021000_39.47.9316.37","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58675"},{"key":"2023041803385021000_39.47.9316.38","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20800"},{"key":"2023041803385021000_39.47.9316.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-07-02459.2000"},{"key":"2023041803385021000_39.47.9316.40","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00758-4"},{"key":"2023041803385021000_39.47.9316.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.11.001"},{"key":"2023041803385021000_39.47.9316.42","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1242\/dev.116.1.201","article-title":"NeuN, a neuronal specific nuclear protein in vertebrates","volume":"116","author":"Mullen","year":"1992","journal-title":"Development"},{"key":"2023041803385021000_39.47.9316.43","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200504029"},{"key":"2023041803385021000_39.47.9316.44","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-6-36"},{"key":"2023041803385021000_39.47.9316.45","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4117-10.2010"},{"key":"2023041803385021000_39.47.9316.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.12.008"},{"key":"2023041803385021000_39.47.9316.47","doi-asserted-by":"crossref","unstructured":"Richner M , Jager SB , Siupka P , Vaegter CB (2017) Hydraulic extrusion of the spinal cord and isolation of dorsal root ganglia in rodents. J Vis Exp 119.","DOI":"10.3791\/55226-v"},{"key":"2023041803385021000_39.47.9316.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.025"},{"key":"2023041803385021000_39.47.9316.49","doi-asserted-by":"publisher","DOI":"10.1002\/neu.10267"},{"key":"2023041803385021000_39.47.9316.50","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-007-0165-6"},{"key":"2023041803385021000_39.47.9316.51","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81795-X"},{"key":"2023041803385021000_39.47.9316.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.11.007"},{"key":"2023041803385021000_39.47.9316.53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4155-10.2010"},{"key":"2023041803385021000_39.47.9316.54","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(85)90360-4"},{"key":"2023041803385021000_39.47.9316.55","doi-asserted-by":"publisher","DOI":"10.1038\/nature01273"},{"key":"2023041803385021000_39.47.9316.56","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1340605"},{"key":"2023041803385021000_39.47.9316.57","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.R115.053751"},{"key":"2023041803385021000_39.47.9316.58","unstructured":"Watson C , Paxinos G , Kayalioglu G , Christopher and Dana Reeve Foundation, ScienceDirect (2009) The spinal cord: a Christopher and Dana Reeve Foundation text and atlas (online service), Ed 1, pp xv, 387. Amsterdam: Elsevier\/Academic."},{"key":"2023041803385021000_39.47.9316.59","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200703055"},{"key":"2023041803385021000_39.47.9316.60","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00835-8"},{"key":"2023041803385021000_39.47.9316.61","doi-asserted-by":"publisher","DOI":"10.1242\/dev.089524"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.0648-19.2019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T07:48:00Z","timestamp":1681804080000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.0648-19.2019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,2]]},"references-count":61,"journal-issue":{"issue":"47","published-online":{"date-parts":[[2019,11,20]]},"published-print":{"date-parts":[[2019,11,20]]}},"alternative-id":["10.1523\/JNEUROSCI.0648-19.2019"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.0648-19.2019","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,2]]}}}