{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:17:17Z","timestamp":1785428237264,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,21]]},"group-title":"Neuroscience","reference-count":81,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R00NS097627"],"award-info":[{"award-number":["R00NS097627"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Startup funding, UROP, and SURP awards"],"award-info":[{"award-number":["Startup funding, UROP, and SURP awards"]}],"id":[{"id":"https:\/\/ror.org\/04gyf1771","id-type":"ROR","asserted-by":"publisher"}]},{"name":"US Department of Education GAANN","award":["P200A220015"],"award-info":[{"award-number":["P200A220015"]}]},{"id":[{"id":"https:\/\/ror.org\/01nebar93","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P40OD018537"],"award-info":[{"award-number":["P40OD018537"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10OD032327"],"award-info":[{"award-number":["S10OD032327"]}],"id":[{"id":"https:\/\/ror.org\/00fj8a872","id-type":"ROR","asserted-by":"publisher"}]},{"id":[{"id":"https:\/\/ror.org\/02g98ya79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Neuronal dendrites can be injured by a number of insults, but the cellular mechanism by which dendrites respond to tissue injury and undergo repair is poorly understood. Much of the field\u2019s progress has evaluated dendrite regeneration following laser injury. While precise, laser injury does not accurately model the real-world damage to surrounding tissue that would accompany neuronal injury. Here, we modify a pinch injury technique to injure both the dendrites and their surrounding tissues in\n                  <jats:italic>Drosophila melanogaster<\/jats:italic>\n                  larvae, more similar to what is observed in real-world injury. We refined this technique such that only half of a sensory neuron\u2019s dendrites are injured, leaving the other half uninjured. Our data indicate that both dynamic and stable dendritic arbors regrow dendrites following pinch injury. Neurons primarily engage in compensatory regeneration whereby new branches are added on the uninjured half of the arbor. Comparing the regenerative response following pinch versus laser injury revealed that dendrites preferentially regrew into areas where the surrounding tissue was left intact, and not into areas where the surrounding tissue was damaged by pinch. These results prompted us to evaluate the damage sustained to surrounding tissue. In examining non-neuronal tissues after pinch injury, we found damage to epidermal cells and the ECM, but not glia. We also observed a robust immune response on the pinched half of the arbor. We conclude that the sustained damage to surrounding tissue and the initiation of an immune response create a non-permissive environment for dendrite regeneration following pinch injury.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>Neuronal dendrites are injured in clinical conditions, such as stroke, traumatic brain injury, and neonatal hypoxia. Dendrites also degenerate in the early stages of a number of neurodegenerative diseases. The role of surrounding tissues in dendrite regeneration is poorly characterized, especially considering that neuronal injury is typically accompanied by broad tissue damage. Our data evaluates dendrite regeneration following an injury that better mirrors real-world conditions and demonstrates that broad tissue damage diminishes a neuron\u2019s capacity to regenerate its dendrites. Our findings show that neurons preferentially regrow into intact, undamaged tissue environments, addressing a large gap in the field\u2019s knowledge: how damage to the surrounding tissue limits neuron regeneration after injury.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Visual Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"738747v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.15.738747","type":"posted-content","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:30:26Z","timestamp":1784640626000},"source":"Crossref","is-referenced-by-count":0,"title":["Epidermal and ECM Damage Following Pinch Injury Restricts Dendrite Regeneration in\n                  <i>Drosophila<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0406-6373","authenticated-orcid":false,"given":"Mia A","family":"Brantley","sequence":"first","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avantika","family":"Pandiyan","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie C","family":"Danh","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7405-8083","authenticated-orcid":false,"given":"Sydney E","family":"Prange","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7580-872X","authenticated-orcid":false,"given":"Dario S","family":"Rimicci","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4200-3870","authenticated-orcid":false,"given":"Katherine L","family":"Thompson-Peer","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA"},{"name":"Center for the Neurobiology of Learning and Memory, Irvine, CA, USA"},{"name":"Sue and Bill Gross Stem Cell Research Center, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072308501526000_2026.07.15.738747v1.1","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.3390\/biomedicines10123186","article-title":"Axonal regeneration: underlying molecular mechanisms and potential therapeutic targets","volume":"10","year":"2022","journal-title":"Biomedicines"},{"key":"2026072308501526000_2026.07.15.738747v1.2","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1007\/s12035-016-9801-x","article-title":"Matrix metalloproteinases during axonal regeneration, a multifactorial role from start to finish","volume":"54","year":"2017","journal-title":"Molecular neurobiology"},{"key":"2026072308501526000_2026.07.15.738747v1.3","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152371"},{"key":"2026072308501526000_2026.07.15.738747v1.4","doi-asserted-by":"crossref","first-page":"1166146","DOI":"10.3389\/fnagi.2023.1166146","article-title":"A nerve-wracking buzz: lessons from Drosophila models of peripheral neuropathy and axon degeneration","volume":"15","year":"2023","journal-title":"Frontiers in Aging Neuroscience"},{"key":"2026072308501526000_2026.07.15.738747v1.5","doi-asserted-by":"crossref","first-page":"e1010127","DOI":"10.1371\/journal.pgen.1010127","article-title":"Dendrite regeneration in C. elegans is controlled by the RAC GTPase CED-10 and the RhoGEF TIAM-1","volume":"18","year":"2022","journal-title":"PLoS genetics"},{"key":"2026072308501526000_2026.07.15.738747v1.6","doi-asserted-by":"crossref","unstructured":"Burra S , Wang Y , Brock AR , Galko MJ (2013) Using Drosophila larvae to study epidermal wound closure and inflammation. 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