{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:56:10Z","timestamp":1782924970633,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,29]]},"reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["EY017061"],"award-info":[{"award-number":["EY017061"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["EY018868"],"award-info":[{"award-number":["EY018868"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["EY025933"],"award-info":[{"award-number":["EY025933"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>M\u00fcller glia possess latent regenerative potential that could be harnessed to restore retinal neurons lost to injury or disease. Although fibroblast growth factor (FGF) signaling is upregulated following retinal damage, its role in mammalian retinal regeneration remains unclear. Here, we investigated the function of FGF signaling in M\u00fcller glial reprogramming using genetic, pharmacological, and single-cell transcriptomic approaches. Activation of FGF signaling alone was insufficient to induce M\u00fcller glial proliferation in the mouse retina. However, conditional deletion of FGFR1\/2 in M\u00fcller glia abolished regenerative responses induced by multiple independent pathways, demonstrating that FGF signaling is essential for regenerative competence. Mechanistically, loss of FGF signaling impaired sustained ERK\/MAPK activation following injury, while MEK\/ERK inhibition phenocopied the regenerative defect. Conversely, constitutive MEK activation induced limited M\u00fcller glial proliferation in the absence of injury. Although STAT3\/5 inhibition synergized with Activin-A to promote robust proliferation and neurogenic gene expression, it failed to rescue regeneration in FGF-deficient M\u00fcller glia. Single-cell RNA sequencing revealed that FGF signaling suppresses multiple anti-regenerative programs, including Hes1, S1pr1, p27, NF-\u03baB, and p300\/CBP activity. Together, these findings identify FGF signaling as a critical permissive regulator of mammalian retinal regeneration that potentiates M\u00fcller glia through sustained ERK activation and suppression of transcriptional barriers to regeneration.<\/jats:p>","DOI":"10.64898\/2026.06.26.731914","type":"posted-content","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:20:13Z","timestamp":1782742813000},"source":"Crossref","is-referenced-by-count":0,"title":["FGF Signaling Potentiates M\u00fcller Glia for Mammalian Retinal Regeneration"],"prefix":"10.64898","author":[{"given":"Neoklis","family":"Makrides","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kissner","sequence":"additional","affiliation":[{"name":"Columbia Stem Cell Initiative, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Peregrin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Hannan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-0825","authenticated-orcid":false,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Columbia University, New York, NY, USA"},{"name":"Department of Pathology and Cell Biology, Columbia University, New York, NY, 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