{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:24:47Z","timestamp":1790101487770,"version":"4.0.1"},"posted":{"date-parts":[[2025,10,2]]},"group-title":"Neuroscience","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R21NS135769"],"award-info":[{"award-number":["R21NS135769"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Bryon Riesch Foundation, Milwaukee, US"},{"id":[{"id":"https:\/\/ror.org\/0430rna51","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Neurons in the central nervous system (CNS) display a high capacity for axon growth during early development but lose this ability at a pivotal differentiation stage marked by synaptic maturation, circuit integration, and a profound shift in gene transcription. Once mature, most CNS neurons fail to reverse this transcriptional switch after axon injury, fundamentally constraining their intrinsic capacity for axon regeneration. Here, we show with single-nucleus RNA sequencing that forced expression of the transcription factor Sox11 in mature corticospinal tract (CST) neurons produces large-scale and stable changes in gene expression that are highly enriched for growth-relevant processes, and which strongly resemble those of pre-synaptic embryonic stages. Moreover, Sox11 is equally effective when delivered to chronically injured CST neurons. These data reveal the ability of Sox11 to reverse a critical step of neuronal maturation even in otherwise unperturbed neurons, clarifying the transcriptional underpinnings and highlighting the potential of Sox11 to act as a pro-regenerative stimulus.<\/jats:p>","DOI":"10.1101\/2025.09.30.679327","type":"posted-content","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T14:20:11Z","timestamp":1759414811000},"source":"Crossref","is-referenced-by-count":1,"title":["Sox11 overexpression restores embryonic pro-growth transcription in mature corticospinal tract neurons"],"prefix":"10.64898","author":[{"given":"Elizabeth","family":"Batsel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Otten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabia","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Pascual","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darby","family":"O\u2019Shea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Rosas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantelis","family":"Tsoulfas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murray G.","family":"Blackmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025100604350644000_2025.09.30.679327v1.1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902820304"},{"key":"2025100604350644000_2025.09.30.679327v1.2","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20224"},{"key":"2025100604350644000_2025.09.30.679327v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.04.022"},{"key":"2025100604350644000_2025.09.30.679327v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-024-00849-3"},{"key":"2025100604350644000_2025.09.30.679327v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.10.007"},{"key":"2025100604350644000_2025.09.30.679327v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.036"},{"key":"2025100604350644000_2025.09.30.679327v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01123-4"},{"key":"2025100604350644000_2025.09.30.679327v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.026"},{"key":"2025100604350644000_2025.09.30.679327v1.9","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-16-1"},{"key":"2025100604350644000_2025.09.30.679327v1.10","first-page":"1","article-title":"Genome-wide chromatin accessibility analyses provide a map for enhancing optic nerve regeneration","volume":"11","year":"2021","journal-title":"Scientific Reports"},{"key":"2025100604350644000_2025.09.30.679327v1.11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1663-15.2015"},{"key":"2025100604350644000_2025.09.30.679327v1.12","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.22489"},{"key":"2025100604350644000_2025.09.30.679327v1.13","doi-asserted-by":"publisher","DOI":"10.1101\/gad.403406"},{"key":"2025100604350644000_2025.09.30.679327v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199710)210:2<79::AID-AJA1>3.0.CO;2-6"},{"key":"2025100604350644000_2025.09.30.679327v1.15","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-29-09675.2003"},{"key":"2025100604350644000_2025.09.30.679327v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.034"},{"key":"2025100604350644000_2025.09.30.679327v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2020.07.026"},{"key":"2025100604350644000_2025.09.30.679327v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41695-z"},{"key":"2025100604350644000_2025.09.30.679327v1.19","doi-asserted-by":"crossref","unstructured":"Hu, M. & Veldman, M. B . Srebf2 mediates successful optic nerve axon regeneration via the mevalonate synthesis pathway. Molecular Neurodegeneration 20, (2025).","DOI":"10.1186\/s13024-025-00807-2"},{"key":"2025100604350644000_2025.09.30.679327v1.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.1161566"},{"key":"2025100604350644000_2025.09.30.679327v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron"},{"key":"2025100604350644000_2025.09.30.679327v1.22","doi-asserted-by":"crossref","unstructured":"Li, Y. , Struebing, F. L. , Wang, J. , King, R. & Geisert, E. E . Different Effect of Sox11 in Retinal Ganglion Cells Survival and Axon Regeneration. Front Genet 0, 633 (2018).","DOI":"10.3389\/fgene.2018.00633"},{"key":"2025100604350644000_2025.09.30.679327v1.23","first-page":"43","article-title":"Sox11 transcription factor modulates peripheral nerve regeneration in adult mice","volume":"1256","year":"2008","journal-title":"Brain Res"},{"key":"2025100604350644000_2025.09.30.679327v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.05.035"},{"key":"2025100604350644000_2025.09.30.679327v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.10.005"},{"key":"2025100604350644000_2025.09.30.679327v1.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1508-24.2024"},{"key":"2025100604350644000_2025.09.30.679327v1.27","doi-asserted-by":"crossref","first-page":"148368","DOI":"10.1016\/j.brainres.2023.148368","article-title":"Experimental gene expression of developmentally downregulated Crmp1, Crmp4, and Crmp5 promotes axon regeneration and retinal ganglion cell survival after optic nerve injury","volume":"1809","year":"2023","journal-title":"Brain Res"},{"key":"2025100604350644000_2025.09.30.679327v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2010.02.002"},{"key":"2025100604350644000_2025.09.30.679327v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.10.005"},{"key":"2025100604350644000_2025.09.30.679327v1.30","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-018-0445-1"},{"key":"2025100604350644000_2025.09.30.679327v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-33011-7"},{"key":"2025100604350644000_2025.09.30.679327v1.32","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.stemcr.2023.02.012","article-title":"Viral delivery of L1CAM promotes axonal extensions by embryonic cerebral grafts in mouse brain","volume":"18","year":"2023","journal-title":"Stem Cell Reports"},{"key":"2025100604350644000_2025.09.30.679327v1.33","doi-asserted-by":"crossref","unstructured":"Beccari, M. S. et al. Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin. Proc Natl Acad Sci U S A 122, (2025).","DOI":"10.1073\/pnas.2502294122"},{"key":"2025100604350644000_2025.09.30.679327v1.34","first-page":"1","article-title":"SOX11 and SOX4 drive the reactivation of an embryonic gene program during murine wound repair","volume":"10","year":"2019","journal-title":"Nature Communications"},{"key":"2025100604350644000_2025.09.30.679327v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(98)00168-0"},{"key":"2025100604350644000_2025.09.30.679327v1.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1197-22.2022"},{"key":"2025100604350644000_2025.09.30.679327v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2200-5"},{"key":"2025100604350644000_2025.09.30.679327v1.38","doi-asserted-by":"publisher","DOI":"10.1101\/2024.09.09.612115"},{"key":"2025100604350644000_2025.09.30.679327v1.39","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/dneu.22780","article-title":"Axon growth and synaptic function: A balancing act for axonal regeneration and neuronal circuit formation in CNS trauma and disease","volume":"80","year":"2020","journal-title":"Dev Neurobiol"},{"key":"2025100604350644000_2025.09.30.679327v1.40","doi-asserted-by":"publisher","DOI":"10.1242\/dev.148312"},{"key":"2025100604350644000_2025.09.30.679327v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2016.12.005"},{"key":"2025100604350644000_2025.09.30.679327v1.42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1131-22.2022"},{"key":"2025100604350644000_2025.09.30.679327v1.43","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-013-0979-2"},{"key":"2025100604350644000_2025.09.30.679327v1.44","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1294.015"},{"key":"2025100604350644000_2025.09.30.679327v1.45","doi-asserted-by":"crossref","unstructured":"Li, Y. et al. SCG10 is required for peripheral axon maintenance and regeneration in mice. J Cell Sci 136, (2023).","DOI":"10.1242\/jcs.260490"},{"key":"2025100604350644000_2025.09.30.679327v1.46","doi-asserted-by":"crossref","unstructured":"El Amri, M. , Pandit, A. & Schlosser, G. Marcks and Marcks-like 1 proteins promote spinal cord development and regeneration in Xenopus. Elife 13, (2024).","DOI":"10.7554\/eLife.98277"},{"key":"2025100604350644000_2025.09.30.679327v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.06.002"},{"key":"2025100604350644000_2025.09.30.679327v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2195-y"},{"key":"2025100604350644000_2025.09.30.679327v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35677-5"},{"key":"2025100604350644000_2025.09.30.679327v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.06.015"},{"key":"2025100604350644000_2025.09.30.679327v1.51","doi-asserted-by":"crossref","unstructured":"Wang, X. W. et al. Histone methyltransferase Ezh2 coordinates mammalian axon regeneration via regulation of key regenerative pathways. J Clin Invest 134, (2023).","DOI":"10.1172\/JCI163145"},{"key":"2025100604350644000_2025.09.30.679327v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-398309-1.00004-4"},{"key":"2025100604350644000_2025.09.30.679327v1.53","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2832-14.2015"},{"key":"2025100604350644000_2025.09.30.679327v1.54","doi-asserted-by":"crossref","unstructured":"Silver, J. , Schwab, M. E. & Popovich, P. G . Central Nervous System Regenerative Failure: Role of Oligodendrocytes, Astrocytes, and Microglia. Cold Spring Harb Perspect Biol 7, a020602 (2015).","DOI":"10.1101\/cshperspect.a020602"},{"key":"2025100604350644000_2025.09.30.679327v1.55","doi-asserted-by":"publisher","DOI":"10.1007\/S11064-019-02844-Y"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.09.30.679327","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:02:27Z","timestamp":1782277347000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.09.30.679327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,2]]},"references-count":55,"URL":"https:\/\/doi.org\/10.1101\/2025.09.30.679327","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1038\/s41598-025-33479-5","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,10,2]]},"subtype":"preprint"}}