{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:03:31Z","timestamp":1791205411525,"version":"4.1.0"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T00:00:00Z","timestamp":1775088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["Christoforidou\/Nov24\/2494-793"],"award-info":[{"award-number":["Christoforidou\/Nov24\/2494-793"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["Christoforidou\/Nov24\/2494-793"],"award-info":[{"award-number":["Christoforidou\/Nov24\/2494-793"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["Christoforidou\/Nov24\/2494-793"],"award-info":[{"award-number":["Christoforidou\/Nov24\/2494-793"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["Dupuis\/Apr16\/852-791"],"award-info":[{"award-number":["Dupuis\/Apr16\/852-791"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["Dupuis\/Apr16\/852-791"],"award-info":[{"award-number":["Dupuis\/Apr16\/852-791"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Impaired cytoplasmic dynein function has been implicated in amyotrophic lateral sclerosis (ALS) pathogenesis, yet the contributions of spinal interneurons to disease phenotypes remain unclear. We tested the hypothesis that hypomorphic dynein function in cholinergic neurons disrupts the development, survival, or positioning of inhibitory interneuron populations in the lumbar spinal cord. Using ChAT-Cre recombination, we generated four mouse genotypes with graded reductions in dynein activity in ChAT\n                    <jats:sup>+<\/jats:sup>\n                    cells:\n                    <jats:italic>Dync1h1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    (wildtype),\n                    <jats:italic>Dync1h1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/+<\/jats:italic>\n                    <\/jats:sup>\n                    (hemizygous wildtype),\n                    <jats:italic>Dync1h1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/Loa<\/jats:italic>\n                    <\/jats:sup>\n                    (heterozygous Loa mutation), and\n                    <jats:italic>Dync1h1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/Loa<\/jats:italic>\n                    <\/jats:sup>\n                    (hemizygous Loa). At 52 weeks of age, lumbar spinal cords (L3\u2013L6) were harvested, cryosectioned, and immunostained for ChAT, GAD-67, Parvalbumin, and Calbindin. Cell counts were performed on confocal images from eight sections per mouse (N\u2009=\u20093 male mice\/genotype), and radial distances from the central canal were normalised to gray matter width. Angular distributions were analysed\n                    <jats:italic>via<\/jats:italic>\n                    circular statistics. There were no significant genotype-dependent differences in the numbers of ChAT\n                    <jats:sup>+<\/jats:sup>\n                    , GAD-67\n                    <jats:sup>+<\/jats:sup>\n                    , Parvalbumin\n                    <jats:sup>+<\/jats:sup>\n                    , or Calbindin\n                    <jats:sup>+<\/jats:sup>\n                    cells, nor in ChAT\n                    <jats:sup>+<\/jats:sup>\n                    subpopulations (motor neurons versus interneurons) or double\u2010positive interneuron subsets (e.g., ChAT\n                    <jats:sup>+<\/jats:sup>\n                    \u2013GAD-67\n                    <jats:sup>+<\/jats:sup>\n                    , Parvalbumin\n                    <jats:sup>+<\/jats:sup>\n                    \u2013GAD-67\n                    <jats:sup>+<\/jats:sup>\n                    , Parvalbumin\n                    <jats:sup>+<\/jats:sup>\n                    \u2013Calbindin\n                    <jats:sup>+<\/jats:sup>\n                    ). Radial positioning relative to the central canal was similarly preserved across all markers and genotypes. Circular\u2010median tests revealed statistically significant shifts in mean angle for ChAT\n                    <jats:sup>+<\/jats:sup>\n                    , GAD-67\n                    <jats:sup>+<\/jats:sup>\n                    , and certain double\u2010positive cells, but these amounted to only 5\u201310\u00b0 displacements, translating to lateral shifts of ~10\u201320 \u00b5m, well within single laminar bands, and are unlikely to impact circuit connectivity. Despite substantial motor deficits and hallmark TDP-43 pathology previously seen in these models, impaired dynein function does not precipitate interneuron loss or gross migratory defects in the lumbar spinal cord. Instead, our findings suggest that the primary contributions of dynein to ALS-like phenotypes likely arise from functional disruptions in axonal transport, synaptic maintenance, and neuronal physiology rather than from structural alterations or loss of interneuron populations.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0346246","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:38:08Z","timestamp":1775151488000},"page":"e0346246","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impaired dynein function preserves spinal interneuron survival and positioning in an ALS-like mouse model"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9352-4908","authenticated-orcid":true,"given":"Eleni","family":"Christoforidou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1329-5394","authenticated-orcid":true,"given":"Jordan S.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7630-0091","authenticated-orcid":true,"given":"Fabio A.","family":"Simoes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3157-3798","authenticated-orcid":true,"given":"Raphaelle","family":"Cassel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Dupuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Nigel","family":"Leigh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5262-7150","authenticated-orcid":true,"given":"Majid","family":"Hafezparast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"issue":"10","key":"pone.0346246.ref001","article-title":"Amyotrophic lateral sclerosis: insights and new prospects in disease 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Grabham","year":"2007","journal-title":"J Neurosci"},{"issue":"5620","key":"pone.0346246.ref020","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1126\/science.1083129","article-title":"Mutations in dynein link motor neuron degeneration to defects in retrograde transport","volume":"300","author":"M Hafezparast","year":"2003","journal-title":"Science"},{"issue":"12","key":"pone.0346246.ref021","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/ncb2127","article-title":"A cytoplasmic dynein tail mutation impairs motor processivity","volume":"12","author":"KM Ori-McKenney","year":"2010","journal-title":"Nat Cell Biol"},{"key":"pone.0346246.ref022","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1749-8104-6-26","article-title":"Neuronal migration defects in the Loa dynein mutant mouse","volume":"6","author":"KM Ori-McKenney","year":"2011","journal-title":"Neural 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Simoes","year":"2025","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"pone.0346246.ref026","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1080\/21678421.2023.2239276","article-title":"Aberrant dynein function promotes TDP-43 aggregation and upregulation of p62 in male mice harboring transgenic human TDP-43","volume":"24","author":"E Christoforidou","year":"2023","journal-title":"Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration"},{"issue":"3","key":"pone.0346246.ref027","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3109\/17482968.2011.636050","article-title":"Does interneuronal dysfunction contribute to neurodegeneration in amyotrophic lateral sclerosis?","volume":"13","author":"MR Turner","year":"2012","journal-title":"Amyotroph Lateral Scler"},{"issue":"2","key":"pone.0346246.ref028","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1007\/s12035-017-0392-y","article-title":"Impairments in motor neurons, interneurons and astrocytes contribute to hyperexcitability in ALS: underlying mechanisms and paths to therapy","volume":"55","author":"D Do-Ha","year":"2018","journal-title":"Mol Neurobiol"},{"issue":"12","key":"pone.0346246.ref029","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.3390\/cells9122550","article-title":"How degeneration of cells surrounding motoneurons contributes to amyotrophic lateral sclerosis","volume":"9","author":"R Crab\u00e9","year":"2020","journal-title":"Cells"},{"key":"pone.0346246.ref030","author":"E Christoforidou","year":"2025"},{"key":"pone.0346246.ref031","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neuroscience.2013.01.028","article-title":"HCN4 subunit expression in fast-spiking interneurons of the rat spinal cord and hippocampus","volume":"237","author":"DI Hughes","year":"2013","journal-title":"Neuroscience"},{"issue":"1","key":"pone.0346246.ref032","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0014-4886(86)90161-5","article-title":"Motoneurons of the rat sciatic nerve","volume":"93","author":"JE Swett","year":"1986","journal-title":"Exp Neurol"},{"issue":"15","key":"pone.0346246.ref033","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1523\/JNEUROSCI.1199-21.2022","article-title":"Multiscale computer model of the spinal dorsal horn reveals changes in network processing associated with chronic pain","volume":"42","author":"L Medlock","year":"2022","journal-title":"J Neurosci"},{"issue":"2","key":"pone.0346246.ref034","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neulet.2009.01.054","article-title":"H-reflex down-conditioning greatly increases the number of identifiable GABAergic interneurons in rat ventral horn","volume":"452","author":"Y Wang","year":"2009","journal-title":"Neurosci Lett"},{"key":"pone.0346246.ref035","first-page":"166","article-title":"Distribution of 28 kDa calbindin-immunopositive neurons in the cat spinal cord","volume":"9","author":"N Merkulyeva","year":"2015","journal-title":"Front Neuroanat"},{"issue":"10","key":"pone.0346246.ref036","doi-asserted-by":"crossref","DOI":"10.18637\/jss.v031.i10","article-title":"CircStat: AMATLABToolbox for Circular Statistics","volume":"31","author":"P Berens","year":"2009","journal-title":"J Stat Soft"},{"key":"pone.0346246.ref037","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neuroscience.2012.04.024","article-title":"Diverse populations of intrinsic cholinergic interneurons in the mouse olfactory bulb","volume":"213","author":"K Krosnowski","year":"2012","journal-title":"Neuroscience"},{"key":"pone.0346246.ref038","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.brainres.2016.07.001","article-title":"Co-expression of GAD67 and choline acetyltransferase in neurons in the mouse spinal cord: A focus on lamina X","volume":"1646","author":"J Gotts","year":"2016","journal-title":"Brain Res"},{"issue":"2","key":"pone.0346246.ref039","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/cne.20711","article-title":"Postnatal phenotype and localization of spinal cord V1 derived interneurons","volume":"493","author":"FJ Alvarez","year":"2005","journal-title":"J Comp Neurol"},{"key":"pone.0346246.ref040","doi-asserted-by":"crossref","first-page":"7028","DOI":"10.1038\/ncomms8028","article-title":"Commissural axonal corridors instruct neuronal migration in the mouse spinal cord","volume":"6","author":"C Laumonnerie","year":"2015","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0346246.ref041","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1038\/s41467-021-22691-2","article-title":"Single nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord","volume":"12","author":"MR Alkaslasi","year":"2021","journal-title":"Nat Commun"},{"issue":"12","key":"pone.0346246.ref042","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1038\/nn.2665","article-title":"Kinesin 3 and cytoplasmic dynein mediate interkinetic nuclear migration in neural stem cells","volume":"13","author":"J-W Tsai","year":"2010","journal-title":"Nat Neurosci"},{"key":"pone.0346246.ref043","doi-asserted-by":"crossref","first-page":"106085","DOI":"10.1016\/j.nbd.2023.106085","article-title":"A human dynein heavy chain mutation impacts cortical progenitor cells causing developmental defects, reduced brain size and altered brain architecture","volume":"180","author":"DM Romero","year":"2023","journal-title":"Neurobiol Dis"},{"issue":"3","key":"pone.0346246.ref044","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1002\/humu.22491","article-title":"Novel dynein DYNC1H1 neck and motor domain mutations link distal spinal muscular atrophy and abnormal cortical 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