{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:37:43Z","timestamp":1790937463016,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,4,6]]},"abstract":"<jats:p>\n                    In the developing central nervous system, the cell cycle clock plays a crucial role in determining cell fate specification. A second clock, the circadian oscillator, generates daily rhythms of cell cycle progression. Although these two clocks interact, the mechanisms linking circadian cell cycle progression and cell fate determination are still poorly understood. A convenient system to address this issue is the pineal organ of lower vertebrates, which contains only two neuronal types, photoreceptors and projection neurons. In particular, photoreceptors constitute the core of the pineal circadian system, being able to transduce daily light inputs into the rhythmical production of melatonin. However, the genetic program leading to photoreceptor fate largely remains to be deciphered. Here, we report a previously undescribed function for the homeobox gene\n                    <jats:italic>Bsx<\/jats:italic>\n                    in controlling pineal proliferation and photoreceptor fate in\n                    <jats:italic>Xenopu<\/jats:italic>\n                    s. We show that\n                    <jats:italic>Xenopus Bsx<\/jats:italic>\n                    (\n                    <jats:italic>Xbsx<\/jats:italic>\n                    ) is expressed rhythmically in postmitotic photoreceptor precursors, reaching a peak during the night, with a cycle that is complementary to the daily rhythms of S-phase entry displayed by pineal cells.\n                    <jats:italic>Xbsx<\/jats:italic>\n                    knockdown results in increased night levels of pineal proliferation, whereas activation of a GR-Xbsx protein flattens the daily rhythms of S-phase entry to the lowest level. Furthermore, evidence is presented that\n                    <jats:italic>Xbsx<\/jats:italic>\n                    is necessary and sufficient to promote a photoreceptor fate. Altogether, these data indicate that\n                    <jats:italic>Xbsx<\/jats:italic>\n                    plays a dual role in contributing to shape the profile of the circadian cell cycle progression and in the specification of pineal photoreceptors, thus acting as a unique link between these two events.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1000854107","type":"journal-article","created":{"date-parts":[[2010,3,22]],"date-time":"2010-03-22T22:36:27Z","timestamp":1269297387000},"page":"6352-6357","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":20,"title":["<i>Xenopus Bsx<\/i>\n                    links daily cell cycle rhythms and pineal photoreceptor fate"],"prefix":"10.1073","volume":"107","author":[{"given":"Silvia","family":"D'Autilia","sequence":"first","affiliation":[{"name":"Unita\u2019 di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Universita\u2019 di Pisa, Pisa 56127, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vania","family":"Broccoli","sequence":"additional","affiliation":[{"name":"Stem Cells and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan 20132, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Barsacchi","sequence":"additional","affiliation":[{"name":"Unita\u2019 di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Universita\u2019 di Pisa, Pisa 56127, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Andreazzoli","sequence":"additional","affiliation":[{"name":"Unita\u2019 di Biologia Cellulare e dello Sviluppo, Dipartimento di Biologia, Universita\u2019 di Pisa, Pisa 56127, Italy; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,3,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00632-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdrc.20161"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0748730404269169"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.04.015"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-1097.1997.tb03188.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1562\/0031-8655(2000)071<0758:DACVIS>2.0.CO;2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2003.1303"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1562\/2006-02-24-IR-813","article-title":"A median third eye: Pineal gland retraces evolution of vertebrate photoreceptive organs","volume":"83","author":"Mano H","year":"2007","unstructured":"H Mano, Y Fukada, A median third eye: Pineal gland retraces evolution of vertebrate photoreceptive organs. Photochem Photobiol 83, 11\u201318 (2007).","journal-title":"Photochem Photobiol"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)80045-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.013482"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00452"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-133X(03)00151-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00166-N"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.10.6975"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2003.10.022"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086271"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(99)00109-1"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00723"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80394-3"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1876"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1155"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03479.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00014-9"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12041-008-0073-8"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1111\/j.1471-4159.2007.04947.x","article-title":"REST is a key regulator in brain-specific homeobox gene expression during neuronal differentiation","volume":"103","author":"Park SY","year":"2007","unstructured":"SY Park, JB Kim, YM Han, REST is a key regulator in brain-specific homeobox gene expression during neuronal differentiation. J Neurochem 103, 2565\u20132574 (2007).","journal-title":"J Neurochem"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906382106"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00738-9"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00215-07"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.05.007"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(02)00025-8"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1007\/s00427-006-0109-0","article-title":"Cloning and developmental expression of the Xenopus homeobox gene Xvsx1","volume":"216","author":"D'Autilia S","year":"2006","unstructured":"S D'Autilia, et al., Cloning and developmental expression of the Xenopus homeobox gene Xvsx1. 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