{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:18:49Z","timestamp":1770747529963,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,14]]},"group-title":"Developmental Biology","reference-count":57,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,14]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Mutations in the human Ocular albinism type-1 gene\n                  <jats:italic>OA1<\/jats:italic>\n                  are associated with abnormal retinal pigment epithelium (RPE) melanogenesis and poor binocular vision resulting from misrouting of ipsilateral retinal ganglion cell (iRGC) axons to the brain. We studied the latter using wild-type (WT) and\n                  <jats:italic>Oa1-\/-<\/jats:italic>\n                  mouse eyes. At embryonic stages, the WT RPE-specific Oa1 protein signals through cAMP\/Epac1-Erk2-CREB. Following CREB phosphorylation, a pCREB gradient extends from the RPE to the differentiating retinal amacrine and RGCs. In contrast to WT, the\n                  <jats:italic>Oa1-\/-<\/jats:italic>\n                  RPE and ventral ciliary-margin-zone, a niche for iRGCs, express less pCREB while their retinas have a disrupted pCREB gradient, indicating Oa1\u2019s involvement in pCREB maintenance.\n                  <jats:italic>Oa1-\/-<\/jats:italic>\n                  retinas also show hyperproliferation, enlarged nuclei, reduced differentiation, and fewer newborn amacrine and RGCs than WT retinas. Our results demonstrate that Oa1\u2019s absence leads to reduced binocular vision through a hyperproliferation-associated block in differentiation that impairs neurogenesis. This may affect iRGC axon\u2019s routing to the brain.\n                <\/jats:p>","DOI":"10.1101\/2024.05.14.594013","type":"posted-content","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T22:50:23Z","timestamp":1715727023000},"source":"Crossref","is-referenced-by-count":1,"title":["Decreased CREB phosphorylation impairs embryonic retinal neurogenesis in the\n                  <i>Oa1-\/-<\/i>\n                  mouse model of Ocular albinism"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7585-8381","authenticated-orcid":false,"given":"Sonia","family":"Guha","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9916-8927","authenticated-orcid":false,"given":"Andrew M.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1855-0559","authenticated-orcid":false,"given":"Alejandra","family":"Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2534-6206","authenticated-orcid":false,"given":"Ethan","family":"Mondell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3207-697X","authenticated-orcid":false,"given":"Debora B.","family":"Farber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024051807200559000_2024.05.14.594013v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-13"},{"key":"2024051807200559000_2024.05.14.594013v1.2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-1806"},{"key":"2024051807200559000_2024.05.14.594013v1.3","unstructured":"Lewis, R.A. (1993). Ocular Albinism, X-Linked. In GeneReviews((R)), M.P. Adam , H.H. Ardinger , R.A. Pagon , S.E. Wallace , L.J.H. Bean , K. Stephens , and A. Amemiya , eds."},{"key":"2024051807200559000_2024.05.14.594013v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/12715"},{"key":"2024051807200559000_2024.05.14.594013v1.5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0749.2006.00292.x"},{"key":"2024051807200559000_2024.05.14.594013v1.6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024376"},{"key":"2024051807200559000_2024.05.14.594013v1.7","first-page":"4333","article-title":"Expression pattern of the ocular albinism type 1 (Oa1) gene in the murine retinal pigment epithelium","volume":"41","year":"2000","journal-title":"Invest Ophthalmol Vis 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