{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:14:05Z","timestamp":1773933245149,"version":"3.50.1"},"reference-count":0,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100010434","name":"'la Caixa' Foundation","doi-asserted-by":"crossref","award":["HR21-01212"],"award-info":[{"award-number":["HR21-01212"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Onset of many neurodegenerative and neuromuscular diseases usually starts in adulthood; however, recent advances point toward neurodevelopmental changes as drivers of late neurodegeneration. How early neuropathological features occur in these conditions remains unclear, which is critical for timely therapeutic intervention. Here, we provide evidence that neurodevelopmental axonal defects initiate a motor phenotype in a zebrafish model of spinocerebellar ataxia type 37 (SCA37), a degenerative hereditary condition caused by an ATTTC repeat in the DAB1 gene. We investigated neuronal defects triggered by the embryonic AUUUC repeat RNA and their effects later in life by transiently expressing this RNA in embryos and analyzing innervation and motor function. We found abnormalities in motor neuron axonal outgrowth and muscle innervation. We also discovered disrupted embryonic motor activity and reduced locomotor distance and velocity in late adult zebrafish, demonstrating motor impairment. Moreover, we showed that NOVA2 expression rescues axonal defects, indicating dysfunction of NOVA2-regulated neurodevelopmental processes. Overall, our results establish embryonic expression of the AUUUC repeat RNA as a driver of axonal and synaptic abnormalities, interfering with neuronal circuits and culminating in adult motor dysfunction.<\/jats:p>","DOI":"10.1242\/dmm.052636","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:48:47Z","timestamp":1773924527000},"source":"Crossref","is-referenced-by-count":0,"title":["Embryonic spinocerebellar ataxia type 37 AUUUC repeat RNA causes neurodevelopmental defects in zebrafish"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-3609","authenticated-orcid":false,"given":"Ana F.","family":"Castro","sequence":"first","affiliation":[{"name":"1 Genetics of Cognitive Dysfunction Laboratory, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"2 ICBAS-School of Medicine and Biomedical Sciences Abel Salazar, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-0736","authenticated-orcid":false,"given":"Ana S.","family":"Figueiredo","sequence":"additional","affiliation":[{"name":"1 Genetics of Cognitive Dysfunction Laboratory, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"2 ICBAS-School of Medicine and Biomedical Sciences Abel Salazar, University of Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"given":"Joana R.","family":"Loureiro","sequence":"additional","affiliation":[{"name":"1 Genetics of Cognitive Dysfunction Laboratory, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"given":"Maria M.","family":"Azevedo","sequence":"additional","affiliation":[{"name":"3 Advanced Light Microscopy Platform, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1148-2159","authenticated-orcid":false,"given":"Paula","family":"Sampaio","sequence":"additional","affiliation":[{"name":"3 Advanced Light Microscopy Platform, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1428-0691","authenticated-orcid":false,"given":"Ana M.","family":"Valentim","sequence":"additional","affiliation":[{"name":"4 Laboratory Animal Science, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8591-7138","authenticated-orcid":false,"given":"Jos\u00e9","family":"Bessa","sequence":"additional","affiliation":[{"name":"5 Vertebrate Development and Regeneration Laboratory, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2610-5260","authenticated-orcid":false,"given":"Isabel","family":"Silveira","sequence":"additional","affiliation":[{"name":"1 Genetics of Cognitive Dysfunction Laboratory, IBMC-Institute for Molecular and Cell Biology and i3S-Institute for Research and Innovation in Health Sciences, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]}],"member":"237","published-online":{"date-parts":[[2026,3,19]]},"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052636\/3690671\/dmm052636.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.052636\/3690671\/dmm052636.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:48:48Z","timestamp":1773924528000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/doi\/10.1242\/dmm.052636\/371086\/Embryonic-spinocerebellar-ataxia-type-37-AUUUC"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,19]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1242\/dmm.052636","relation":{},"ISSN":["1754-8403","1754-8411"],"issn-type":[{"value":"1754-8403","type":"print"},{"value":"1754-8411","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,19]]},"article-number":"dmm.052636"}}