{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:17:39Z","timestamp":1785421059461,"version":"3.56.0"},"posted":{"date-parts":[[2025,7,3]]},"group-title":"Neuroscience","reference-count":55,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01EY036173"],"award-info":[{"award-number":["R01EY036173"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The RNA-binding protein Ptbp1 has been proposed as a master regulator of neuronal fate, repressing neurogenesis through its effects on alternative splicing and miRNA maturation. While prior studies using RNA interference suggested that Ptbp1 loss promotes neurogenesis, recent genetic studies have failed to replicate glia-to-neuron conversion following\n                  <jats:italic>Ptbp1<\/jats:italic>\n                  loss of function. To evaluate the role of Ptbp1 in developmental neurogenesis\n                  <jats:italic>in vivo<\/jats:italic>\n                  , we conditionally disrupted\n                  <jats:italic>Ptbp1<\/jats:italic>\n                  in retinal progenitors. Ptbp1 was robustly expressed in both retinal progenitors and M\u00fcller glia but absent from postmitotic neurons, and efficient loss of function in mutant animals was confirmed using immunostaining for Ptbp1. Furthermore, bulk RNA-Seq at E16 revealed accelerated expression of late-stage progenitor and photoreceptor-specific genes and altered splicing patterns in\n                  <jats:italic>Ptbp1<\/jats:italic>\n                  mutants, including increased inclusion of rod photoreceptor-specific exons. However, we observed no defects in retinal lamination, progenitor proliferation, or cell fate specification in mature retina. ScRNA-Seq of mature mutant retinas revealed only modest transcriptional changes which partially recapitulate alterations seen following selective deletion of\n                  <jats:italic>Ptbp1<\/jats:italic>\n                  in mature glia. Our findings demonstrate that Ptbp1 is dispensable for retinal cell fate specification and suggest that its proposed role as a central repressor of neurogenesis should be reevaluated.\n                <\/jats:p>","DOI":"10.1101\/2025.07.02.662808","type":"posted-content","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T23:30:23Z","timestamp":1751585423000},"source":"Crossref","is-referenced-by-count":0,"title":["Ptbp1 is not required for retinal neurogenesis and cell fate specification"],"prefix":"10.64898","author":[{"given":"Haley","family":"Appel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogger P.","family":"Carmen-Orozco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton 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