{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T04:44:24Z","timestamp":1784436264686,"version":"3.55.0"},"reference-count":71,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","award":["PIP 11220200100296"],"award-info":[{"award-number":["PIP 11220200100296"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Circadian rhythm alignment depends on environmental light detection via opsins. Pinopsin, originally identified in the pineal organ of birds and later in amphibian pineal complex and eyes, may play a role in this process, though its function has not been genetically tested. Evolutionary analysis suggests pinopsin was independently lost in several vertebrate lineages, including mammals (Synapsida), some reptiles (e.g. snakes and crocodiles), and teleost fish, but retained in birds, turtles, lizards, and non\u2010teleost Actinopterygii. We conducted a detailed genomic search of the pinopsin gene across 95 amphibian species and assessed its function in\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    tadpoles using CRISPR\/Cas9\u2010mediated knockout. Our survey indicates that pinopsin is highly conserved in salamanders and most anurans, but absent in many caecilians (Gymnophiona), which have a fossorial lifestyle with limited light exposure. To investigate its biological role, we generated\n                    <jats:italic>X. laevis<\/jats:italic>\n                    F0 pinopsin knockout tadpoles and evaluated two light\u2010sensitive responses: (1) day\/night melatonin fluctuations inferred from skin pigmentation changes, and (2) locomotor activity over a 24\u2010h photoperiod. We show these responses depend only on pineal light sensitivity and are independent of eye sensitivity at developmental stage 46\/47. Our findings reveal: (1) Pinopsin is co\u2010expressed with Aanat, a key enzyme in melatonin synthesis; (2) knockout tadpoles show paler skin during the light phase, suggesting pinopsin suppresses melatonin production in daylight; and (3) reduced daytime locomotor activity in F0 mutants, consistent with melatonin\u2010induced lethargy. Overall, pinopsin emerges as a critical opsin for light\u2010regulated circadian\u2010associated behavior in\n                    <jats:italic>Xenopus<\/jats:italic>\n                    , with likely conserved roles across amphibians (anurans and salamanders in general) and other non\u2010mammalian vertebrates, including birds, turtles, and lizards.\n                  <\/jats:p>","DOI":"10.1111\/jpi.70114","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:19:57Z","timestamp":1769512797000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pinopsin Regulates Melatonin Production and Daily Locomotor Activity: Functional Insights From Gene\u2010Edited\n                    <i>Xenopus<\/i>\n                    Tadpoles"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8248-1722","authenticated-orcid":false,"given":"Neda","family":"Heshami","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Anatomy Hotchkiss Brain Institute Calgary Alberta Canada"},{"name":"Department of Cell Biology and Anatomy Alberta Children's Hospital Research Institute Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8316-8379","authenticated-orcid":false,"given":"Ricardo D.","family":"Romero","sequence":"additional","affiliation":[{"name":"Biolog\u00eda Molecular y Neurociencias (IFIBYNE\u2010UBA\u2010CONICET) Instituto de Fisiolog\u00eda Ciudad de Buenos Aires Argentina"},{"name":"Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, (FBMC\u2010FCEyN\u2010UBA), Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires Ciudad de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-2873","authenticated-orcid":false,"given":"Flavio S. J.","family":"de Souza","sequence":"additional","affiliation":[{"name":"Biolog\u00eda Molecular y Neurociencias (IFIBYNE\u2010UBA\u2010CONICET) Instituto de Fisiolog\u00eda Ciudad de Buenos Aires Argentina"},{"name":"Departamento de Fisiolog\u00eda, Biolog\u00eda Molecular y Celular, (FBMC\u2010FCEyN\u2010UBA), Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires Ciudad de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6154-9513","authenticated-orcid":false,"given":"Gabriel E.","family":"Bertolesi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy Hotchkiss Brain Institute Calgary Alberta Canada"},{"name":"Department of Cell Biology and Anatomy Alberta Children's Hospital Research Institute Calgary Alberta 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