Genetic regulation of Wnt/PCP components through Fgf10/Fgfr2/Sox9 module in tear duct development

preprint OA: closed
Full text JSON View at publisher

Abstract

Abstract Fibroblast growth factor (Fgf) and Wnt signaling pathways are essential for diverse aspects of tissue morphogenesis, and their disruption often results in overlapping developmental defects. However, the mechanistic links between these pathways remain poorly defined, and it is unclear whether direct genetic interactions exist during development. In this study, we demonstrate that the Fgf signaling components Fgf10 and Fgfr2 are indispensable for tear duct formation by promoting the proliferation and survival of tear duct progenitors. In addition, Fgf10/Fgfr2 signaling contributes to tear duct elongation. Through single-cell RNA sequencing and CUT&Tag analysis, we provide comprehensive genetic evidence that the Fgf10/Fgfr2/Sox9 module directly regulates a subset of Wnt/planar cell polarity (PCP) genes. In particular, we show that Sox9 binds to and activates the promoter of Prickle1, a core Wnt/PCP component previously implicated in tear duct development. Finally, we establish that the regulation of Wnt/PCP components by Fgf signaling is unidirectional. Together, these findings uncover a previously unrecognized direct genetic link between Fgf signaling and Wnt/PCP pathway components during tear duct morphogenesis.
Full text 16,710 characters · extracted from preprint-html · click to expand
Genetic regulation of Wnt/PCP components through Fgf10/Fgfr2/Sox9 module in tear duct development | 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 Article Genetic regulation of Wnt/PCP components through Fgf10/Fgfr2/Sox9 module in tear duct development Chunqiao Liu, Dianlei Guo, Xiaoyu Zhang, Xinyi Zhao, Jiali Ru, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7980825/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Fibroblast growth factor (Fgf) and Wnt signaling pathways are essential for diverse aspects of tissue morphogenesis, and their disruption often results in overlapping developmental defects. However, the mechanistic links between these pathways remain poorly defined, and it is unclear whether direct genetic interactions exist during development. In this study, we demonstrate that the Fgf signaling components Fgf10 and Fgfr2 are indispensable for tear duct formation by promoting the proliferation and survival of tear duct progenitors. In addition, Fgf10/Fgfr2 signaling contributes to tear duct elongation. Through single-cell RNA sequencing and CUT&Tag analysis, we provide comprehensive genetic evidence that the Fgf10/Fgfr2/Sox9 module directly regulates a subset of Wnt/planar cell polarity (PCP) genes. In particular, we show that Sox9 binds to and activates the promoter of Prickle1, a core Wnt/PCP component previously implicated in tear duct development. Finally, we establish that the regulation of Wnt/PCP components by Fgf signaling is unidirectional. Together, these findings uncover a previously unrecognized direct genetic link between Fgf signaling and Wnt/PCP pathway components during tear duct morphogenesis. Biological sciences/Genetics/Development Biological sciences/Developmental biology/Morphogenesis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementarytables.docx Supplementary table SupplementaryFigureXFigurelegends.pdf Supplementary Figures and Figure legends Cite Share Download PDF Status: Posted Version 1 posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7980825","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":540016765,"identity":"2bc146a5-329e-496b-8a4d-9e07a5ed60cb","order_by":0,"name":"Chunqiao Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDklEQVRIiWNgGAWjYBACPmYGBmYQQ569gYEhoQAmzoZbCxtMi2HPAaAWA2K0MEC1MNxIABJEaWHnMfxc2HZHtnHm68QPDwwY7A3OnzFg+FB2mIF/dgMOh/EYS89se2bcLp27WQLosMQNN3IMGGecO8wgcecALi1mzLxthxMbZ+duAGlJMLjBYwASYTCQSMCvpeHm2c0/EqAOY/5LlJYbvNtAtjBuOJBjwMyIVwtbsTTPucPGG3tyt1kkGEgkzryRVnCw51w6j8QN7Fr4+Q9v/MxTdlh2PvvZzTd/VNjY850/vPHBjzJrOf4Z2LXAAGMDhJZgUDjAwABEDDx41SNpAaacBtyqRsEoGAWjYGQCAI56WP3AHuY/AAAAAElFTkSuQmCC","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":true,"prefix":"","firstName":"Chunqiao","middleName":"","lastName":"Liu","suffix":""},{"id":540016766,"identity":"ce319db6-9ebf-40a0-a0c5-fd6c9121ace3","order_by":1,"name":"Dianlei Guo","email":"","orcid":"","institution":"Sun Yat-Sen University","correspondingAuthor":false,"prefix":"","firstName":"Dianlei","middleName":"","lastName":"Guo","suffix":""},{"id":540016767,"identity":"c534ff3a-40d5-4176-9279-8bfc4ec7d8d5","order_by":2,"name":"Xiaoyu Zhang","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Zhang","suffix":""},{"id":540016768,"identity":"b3c3ccea-5c45-4878-8a7e-9f8c7759ad95","order_by":3,"name":"Xinyi Zhao","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Xinyi","middleName":"","lastName":"Zhao","suffix":""},{"id":540016769,"identity":"2342cef6-9253-45d1-ac2f-f66eac172ed2","order_by":4,"name":"Jiali Ru","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Jiali","middleName":"","lastName":"Ru","suffix":""},{"id":540016770,"identity":"e1713502-0369-443c-bcdb-9928db2613d4","order_by":5,"name":"Mingzhu Guo","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Mingzhu","middleName":"","lastName":"Guo","suffix":""},{"id":540016771,"identity":"abe94b72-aa00-4409-9edc-5a0aaa10eb7a","order_by":6,"name":"Lijing Xie","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Lijing","middleName":"","lastName":"Xie","suffix":""},{"id":540016772,"identity":"54a5ce90-99a1-45a8-a6a1-933a0bfcbd7a","order_by":7,"name":"Mingjuan Wu","email":"","orcid":"","institution":"International Ocular Surface Research Center, Institute of Ophthalmology and Key Laboratory for Regenerative Medicine of the Ministry of Education, Jinan University, Guangzhou","correspondingAuthor":false,"prefix":"","firstName":"Mingjuan","middleName":"","lastName":"Wu","suffix":""},{"id":540016773,"identity":"d7bfc5b5-5116-4f9f-8e5f-e9f05c1750d4","order_by":8,"name":"Lei Shi","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Shi","suffix":""},{"id":540016774,"identity":"ea998b13-4f83-4dc6-a5e8-20739ebe05da","order_by":9,"name":"Yingchun Su","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Yingchun","middleName":"","lastName":"Su","suffix":""},{"id":540016775,"identity":"e81055e5-109d-4774-88c5-ec20544d8481","order_by":10,"name":"Shujuan Xu","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Shujuan","middleName":"","lastName":"Xu","suffix":""},{"id":540016776,"identity":"25ae70ef-f519-4fab-a3a7-7bc460c76009","order_by":11,"name":"Rong Ju","email":"","orcid":"","institution":"Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Rong","middleName":"","lastName":"Ju","suffix":""},{"id":540016777,"identity":"336d43fd-f120-46e1-9a48-9f46da28253c","order_by":12,"name":"Shanzhen Peng","email":"","orcid":"","institution":"Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Shanzhen","middleName":"","lastName":"Peng","suffix":""},{"id":540016778,"identity":"36feecfa-c76f-4e04-b15a-c21da2774223","order_by":13,"name":"Xuri Li","email":"","orcid":"https://orcid.org/0000-0002-8277-0767","institution":"Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Xuri","middleName":"","lastName":"Li","suffix":""},{"id":540016779,"identity":"d969cd81-83f7-4140-8d24-e330a0fb2d56","order_by":14,"name":"Rongxin Chen","email":"","orcid":"","institution":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University","correspondingAuthor":false,"prefix":"","firstName":"Rongxin","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-10-29 14:16:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7980825/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7980825/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":96748129,"identity":"66f28c3d-6b73-4e52-9273-cb9a6c185d33","added_by":"auto","created_at":"2025-11-25 16:17:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":3027696,"visible":true,"origin":"","legend":"","description":"","filename":"Guoetal2025WithFigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7980825/v1/8ad3931ee953fd0cd23d34bd.pdf"},{"id":96748125,"identity":"f5afea02-686f-4cb8-9ac2-e65e44b1886e","added_by":"auto","created_at":"2025-11-25 16:17:57","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":14846,"visible":true,"origin":"","legend":"","description":"","filename":"NCOMMS2586975.json","url":"https://assets-eu.researchsquare.com/files/rs-7980825/v1/f46dd539e8b1aa9ade5e0df7.json"},{"id":96748128,"identity":"9b59e3bb-6a38-4333-8333-3b692339af75","added_by":"auto","created_at":"2025-11-25 16:17:58","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1812496,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigureXFigurelegends.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7980825/v1/bdd5860eb746c9245581dfb0.pdf"},{"id":96748127,"identity":"767aa244-ec63-441d-aa17-9f7648040c2c","added_by":"auto","created_at":"2025-11-25 16:17:58","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":25396,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7980825/v1/edec90eddd78e0773a1dc90d.docx"},{"id":96913763,"identity":"c52d2db4-427b-4674-af30-0c203922d5ee","added_by":"auto","created_at":"2025-11-27 14:04:14","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3083218,"visible":true,"origin":"","legend":"Article File","description":"","filename":"Guoetal2025WithFigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7980825/v1_covered_d78022a2-ff38-4c37-9d92-ebe4f66f9589.pdf"},{"id":96748124,"identity":"e11914ae-9165-428f-b04a-479b16616a30","added_by":"auto","created_at":"2025-11-25 16:17:57","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25396,"visible":true,"origin":"","legend":"Supplementary table","description":"","filename":"Supplementarytables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7980825/v1/cb7df1009f978524342e8d78.docx"},{"id":96748126,"identity":"5741c989-2275-458e-8b49-0e850426e321","added_by":"auto","created_at":"2025-11-25 16:17:58","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":1812496,"visible":true,"origin":"","legend":"Supplementary Figures and Figure legends","description":"","filename":"SupplementaryFigureXFigurelegends.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7980825/v1/6b144c15def1dac0bacacbb8.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Genetic regulation of Wnt/PCP components through Fgf10/Fgfr2/Sox9 module in tear duct development","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7980825/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7980825/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Fibroblast growth factor (Fgf) and Wnt signaling pathways are essential for diverse aspects of tissue morphogenesis, and their disruption often results in overlapping developmental defects. However, the mechanistic links between these pathways remain poorly defined, and it is unclear whether direct genetic interactions exist during development. In this study, we demonstrate that the Fgf signaling components Fgf10 and Fgfr2 are indispensable for tear duct formation by promoting the proliferation and survival of tear duct progenitors. In addition, Fgf10/Fgfr2 signaling contributes to tear duct elongation. Through single-cell RNA sequencing and CUT\u0026Tag analysis, we provide comprehensive genetic evidence that the Fgf10/Fgfr2/Sox9 module directly regulates a subset of Wnt/planar cell polarity (PCP) genes. In particular, we show that Sox9 binds to and activates the promoter of Prickle1, a core Wnt/PCP component previously implicated in tear duct development. Finally, we establish that the regulation of Wnt/PCP components by Fgf signaling is unidirectional. Together, these findings uncover a previously unrecognized direct genetic link between Fgf signaling and Wnt/PCP pathway components during tear duct morphogenesis.","manuscriptTitle":"Genetic regulation of Wnt/PCP components through Fgf10/Fgfr2/Sox9 module in tear duct development","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-25 16:17:53","doi":"10.21203/rs.3.rs-7980825/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d9c42efc-bd11-417b-9e11-eb430bab9e81","owner":[],"postedDate":"November 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57442731,"name":"Biological sciences/Genetics/Development"},{"id":57442732,"name":"Biological sciences/Developmental biology/Morphogenesis"}],"tags":[],"updatedAt":"2025-11-25T16:17:53+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-25 16:17:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7980825","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7980825","identity":"rs-7980825","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00