{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:26:55Z","timestamp":1792787215632,"version":"4.5.0"},"reference-count":74,"publisher":"National Academy of Sciences","issue":"16","license":[{"start":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T00:00:00Z","timestamp":1490659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["103191\/Z\/13\/Z"],"award-info":[{"award-number":["103191\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["107116\/Z\/15\/Z"],"award-info":[{"award-number":["107116\/Z\/15\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["NS054154"],"award-info":[{"award-number":["NS054154"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM088278"],"award-info":[{"award-number":["R01GM088278"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2017,4,18]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>The mechanisms triggering motor and sensory nerve dysfunction in the genetically diverse Charcot\u2013Marie\u2013Tooth disease (CMT) remain unresolved, as does the reason for the lack of sensory pathology observed in distal hereditary motor neuropathies, which can be associated with CMT genes. To unravel the pathways leading to afferent deterioration, we have studied the sensory nervous system of CMT type 2D (CMT2D) mice. Our work demonstrates that the specific cellular identity of sensory nerves is perturbed in mutant mice prenatally, and that this is likely caused by aberrant interaction of mutant CMT2D protein with Trk receptors impacting their prodifferentiation\/development signaling. CMT therefore manifests through malfunctioning of the complex interplay between developmental, maturation, and survival programs, which has important implications for therapeutic timing.<\/jats:p>","DOI":"10.1073\/pnas.1614557114","type":"journal-article","created":{"date-parts":[[2017,3,28]],"date-time":"2017-03-28T20:20:17Z","timestamp":1490732417000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":72,"title":["Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by\n                    <i>Gars<\/i>\n                    mutations"],"prefix":"10.1073","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3782-9045","authenticated-orcid":false,"given":"James N.","family":"Sleigh","sequence":"first","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Dawes","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"West","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Spaulding","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609;"},{"name":"Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME 04469"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"G\u00f3mez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Burgess","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609;"},{"name":"Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME 04469"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Zameel","family":"Cader","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5490-1697","authenticated-orcid":false,"given":"Kevin","family":"Talbot","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-8745","authenticated-orcid":false,"given":"Giampietro","family":"Schiavo","sequence":"additional","affiliation":[{"name":"Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2017,3,28]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2011.00324.x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmrj.2013.08.611"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1974.tb00638.x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/375039"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1727"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.12.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.09.008"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22210"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.11.001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600052"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.08.027"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.002527"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705055104"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703908104"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002399"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104293108"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv176"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature15510"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1200194109"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh590"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000201275.18875.ac"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-010-5491-x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1179\/1743132815Y.0000000055"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00442.x"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.3109\/07853890.2012.665471"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00021"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.03.006"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt659"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015573"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4338-07.2007"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw035"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)90865-0"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902280211"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-02-00555.1988"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90618-L"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23672"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1980-10.2010"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(97)00173-5"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(20000626)422:2<172::AID-CNE2>3.0.CO;2-H"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2014.00293"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906809106"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1762-15.2016"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.01.015"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01187846"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.04.019"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901507106"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.01.030"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0241-15.2015"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.03.006"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80899-5"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(01)00293-0"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83641-4"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/39807"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1996.0030"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201387579"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161629"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-4388(00)00208-7"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960722)371:2<249::AID-CNE5>3.0.CO;2-2"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1299"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-17-07040.1998"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/368246a0"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90213-5"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1283"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1701"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.02.008"},{"key":"e_1_3_3_66_2","first-page":"26","article-title":"Older but not slower: Aging does not alter axonal transport dynamics of signalling endosomes in vivo","volume":"257","author":"Sleigh JN","year":"2016","unstructured":"JN Sleigh, G Schiavo, Older but not slower: Aging does not alter axonal transport dynamics of signalling endosomes in vivo. J Neurosci Methods 257, 26\u201333 (2016).","journal-title":"J Neurosci Methods"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt477"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-016-1915-8"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.461"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"e_1_3_3_71_2","article-title":"Motor coordination and balance in rodents","volume":"8","author":"Carter RJ","year":"2001","unstructured":"RJ Carter, J Morton, SB Dunnett, Motor coordination and balance in rodents. Curr Protoc Neurosci Chapter 8:Unit 8.12 (2001).","journal-title":"Curr Protoc Neurosci"},{"key":"e_1_3_3_72_2","first-page":"409","article-title":"A method for measurement of analgesic activity on inflamed tissue","volume":"111","author":"Randall LO","year":"1957","unstructured":"LO Randall, JJ Selitto, A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther 111, 409\u2013419 (1957).","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(88)90026-7"},{"key":"e_1_3_3_74_2","first-page":"780","article-title":"Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease","volume":"6","author":"Bogdanik LP","year":"2013","unstructured":"LP Bogdanik, , Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease. Dis Model Mech 6, 780\u2013792 (2013).","journal-title":"Dis Model Mech"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1614557114","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1614557114","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T01:47:55Z","timestamp":1649814475000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1614557114"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,28]]},"references-count":74,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2017,4,18]]}},"alternative-id":["10.1073\/pnas.1614557114"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1614557114","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/071159","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.3410\/f.727458357.793533362","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,28]]},"assertion":[{"value":"2017-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}