SCIN affects synaptic development by regulating the entry of β-catenin into the nucleus, leading to core symptoms of autism spectrum disorder

SCIN affects synaptic development by regulating the entry of β-catenin into the nucleus, leading to core symptoms of autism spectrum disorder | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article SCIN affects synaptic development by regulating the entry of β-catenin into the nucleus, leading to core symptoms of autism spectrum disorder Chuxuan Wang, Meng Xu, Sirun Lv, Mingqi Lv, Yan Wang, Lulu Zhang, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8556595/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Background Autism spectrum disorder (ASD) often manifests as social interaction disorders, language development disorders and repetitive stereotyped behaviors. Aberrant development of neuronal synapses and dendritic spines is a commonly studied pathogenetic process. Scinderin (SCIN) is an important actin-binding protein that plays a crucial role in synaptic development. Methods​ A valproic acid (VPA)-induced ASD rat model was established. Behavioral tests, molecular detection (SCIN, Wnt/β-catenin components, PSD95, SYP), and analysis of β-catenin nuclear entry, neuron number, and dendritic spine density were performed. SCIN knockdown via AAV shRNA was used to verify its function.​ Results​ ASD rats showed reduced communication/exploration and increased anxiety. In the prefrontal cortex, SCIN, Wnt/β-catenin components, and β-catenin nuclear entry were upregulated; PSD95, SYP, neuron number, and dendritic spine density were downregulated. SCIN knockdown improved ASD-like behaviors and reversed these molecular/pathological changes. ​ Conclusions​ SCIN regulates synaptic development via modulating β-catenin nuclear entry, thereby affecting ASD core symptoms. This study provides new pathogenic insights and identifies SCIN as a potential therapeutic target for ASD.​ Autism spectrum disorder synaptic development SCIN β-catenin Wnt signaling pathway Full Text Additional Declarations No competing interests reported. Supplementary Files Supplementaryfigures.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 01 Apr, 2026 Reviews received at journal 29 Mar, 2026 Reviews received at journal 27 Mar, 2026 Reviewers agreed at journal 15 Mar, 2026 Reviewers agreed at journal 13 Mar, 2026 Reviewers invited by journal 08 Feb, 2026 Editor assigned by journal 12 Jan, 2026 Submission checks completed at journal 12 Jan, 2026 First submitted to journal 08 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8556595","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":588352847,"identity":"78318488-cc9b-4b0a-a1e7-bce3d4c71f44","order_by":0,"name":"Chuxuan Wang","email":"","orcid":"","institution":"Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chuxuan","middleName":"","lastName":"Wang","suffix":""},{"id":588352852,"identity":"eccfb364-b534-4af9-a60c-12d6d642b3d2","order_by":1,"name":"Meng Xu","email":"","orcid":"","institution":"Chongqing Medical 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disorder","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurodevelopmental-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jndd","sideBox":"Learn more about [Journal of Neurodevelopmental Disorders](http://jneurodevdisorders.biomedcentral.com/)","snPcode":"11689","submissionUrl":"https://submission.nature.com/new-submission/11689/3","title":"Journal of Neurodevelopmental Disorders","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Autism spectrum disorder, synaptic development, SCIN, β-catenin, Wnt signaling pathway","lastPublishedDoi":"10.21203/rs.3.rs-8556595/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8556595/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAutism spectrum disorder (ASD) often manifests as social interaction disorders, language development disorders and repetitive stereotyped behaviors. Aberrant development of neuronal synapses and dendritic spines is a commonly studied pathogenetic process. Scinderin (SCIN) is an important actin-binding protein that plays a crucial role in synaptic development.\u003c/p\u003e\u003ch2\u003eMethods​\u003c/h2\u003e \u003cp\u003eA valproic acid (VPA)-induced ASD rat model was established. Behavioral tests, molecular detection (SCIN, Wnt/β-catenin components, PSD95, SYP), and analysis of β-catenin nuclear entry, neuron number, and dendritic spine density were performed. SCIN knockdown via AAV shRNA was used to verify its function.​\u003c/p\u003e\u003ch2\u003eResults​\u003c/h2\u003e \u003cp\u003eASD rats showed reduced communication/exploration and increased anxiety. In the prefrontal cortex, SCIN, Wnt/β-catenin components, and β-catenin nuclear entry were upregulated; PSD95, SYP, neuron number, and dendritic spine density were downregulated. SCIN knockdown improved ASD-like behaviors and reversed these molecular/pathological changes.\u003cb\u003e​\u003c/b\u003e\u003c/p\u003e\u003ch2\u003eConclusions​\u003c/h2\u003e \u003cp\u003eSCIN regulates synaptic development via modulating β-catenin nuclear entry, thereby affecting ASD core symptoms. This study provides new pathogenic insights and identifies SCIN as a potential therapeutic target for ASD.​\u003c/p\u003e","manuscriptTitle":"SCIN affects synaptic development by regulating the entry of β-catenin into the nucleus, leading to core symptoms of autism spectrum disorder","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-12 16:50:36","doi":"10.21203/rs.3.rs-8556595/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-01T20:11:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-30T01:10:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-27T16:18:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285975339460442150624341433551248083827","date":"2026-03-16T01:25:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"108881334909155678224641724429659000305","date":"2026-03-13T06:57:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-08T17:15:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-12T08:49:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-12T08:46:07+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Neurodevelopmental Disorders","date":"2026-01-09T03:57:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neurodevelopmental-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jndd","sideBox":"Learn more about [Journal of Neurodevelopmental Disorders](http://jneurodevdisorders.biomedcentral.com/)","snPcode":"11689","submissionUrl":"https://submission.nature.com/new-submission/11689/3","title":"Journal of Neurodevelopmental Disorders","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d2d97404-9ca4-4d05-887f-8640c7b08859","owner":[],"postedDate":"February 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-01T20:26:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-12 16:50:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8556595","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8556595","identity":"rs-8556595","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}