{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:45:22Z","timestamp":1775933122603,"version":"3.50.1"},"posted":{"date-parts":[[2025,2,25]]},"group-title":"Developmental Biology","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Lens vesicle closure is a pivotal event in ocular morphogenesis, and its disruption underlies Peters anomaly, a leading congenital cause of corneal opacity. Here, we elucidate a mechanistic hierarchy in which mTOR-Wnt signaling orchestrates cytoskeletal tension to drive this process. Conditional ablation of mTOR in the lens ectoderm induces aberrant corneal-lenticular stalk formation and transdifferentiation of the ciliary margin into neural retina. mTOR inhibition suppresses Wnt3 expression, and Wnt3 displayed a similar lens stalk phenotype, positioning mTOR as an upstream regulator of Wnt ligand production. Complete ablation of lens-derived Wnt ligands via deletion of the Wnt transporter Wls exacerbates developmental defects, triggering anterior lens herniation and ciliary margin development failure. Disruption of \u03b2-catenin-mediated Wnt signaling or dual deletion of Wnt co-receptors Lrp5\/6 in lens ectoderm similarly prevents vesicle closure, recapitulating lens herniation. Strikingly, Rac1 deletion rescues corneal-lenticular stalk phenotypes in mTOR, Wls, and \u03b2-catenin mutants, directly linking Wnt effectors to cytoskeletal remodeling. Our findings establish an mTOR-Wnt-Rac1 signaling axis as the core regulator of cytoskeletal tension required for lens vesicle closure.<\/jats:p>","DOI":"10.1101\/2025.02.24.639869","type":"posted-content","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T17:10:47Z","timestamp":1740503447000},"source":"Crossref","is-referenced-by-count":0,"title":["mTOR regulates Wnt signaling to promote tension-mediated lens vesicle closure"],"prefix":"10.64898","author":[{"given":"Qian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingyu","family":"Mao","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyssa","family":"Chow","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bouaziz","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-0825","authenticated-orcid":false,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Pathology and Cell Biology, Columbia University, New York, NY 10032, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041111040186000_2025.02.24.639869v1.1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.184000"},{"key":"2026041111040186000_2025.02.24.639869v1.2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj9846"},{"key":"2026041111040186000_2025.02.24.639869v1.3","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1044903"},{"key":"2026041111040186000_2025.02.24.639869v1.4","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e31820156a9"},{"key":"2026041111040186000_2025.02.24.639869v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2008.07.002"},{"key":"2026041111040186000_2025.02.24.639869v1.6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.436865"},{"key":"2026041111040186000_2025.02.24.639869v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.12.038"},{"key":"2026041111040186000_2025.02.24.639869v1.8","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr014"},{"key":"2026041111040186000_2025.02.24.639869v1.9","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120022"},{"key":"2026041111040186000_2025.02.24.639869v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.012"},{"key":"2026041111040186000_2025.02.24.639869v1.11","doi-asserted-by":"crossref","unstructured":"Cvekl, A. , Zhang, X. , 2017. 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