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A specific set of homeobox gene\u2010encoded transcription factors govern pineal development, and some are expressed in adulthood. The brain\u2010specific homeobox gene (\n                    <jats:italic>Bsx<\/jats:italic>\n                    ) falls into both categories. We here examined regulation and function of\n                    <jats:italic>Bsx<\/jats:italic>\n                    in the mature pineal gland of the rat. We report that\n                    <jats:italic>Bsx<\/jats:italic>\n                    is expressed from prenatal stages into adulthood, where\n                    <jats:italic>Bsx<\/jats:italic>\n                    transcripts are localized in the melatonin\u2010synthesizing pinealocytes, as revealed by RNAscope in situ hybridization.\n                    <jats:italic>Bsx<\/jats:italic>\n                    transcripts were also detected in the adult human pineal gland. In the rat pineal gland,\n                    <jats:italic>Bsx<\/jats:italic>\n                    was found to exhibit a 10\u2010fold circadian rhythm with a peak at night. By combining in vivo adrenergic stimulation and surgical denervation of the gland in the rat with in vitro stimulation and transcriptional inhibition in cultured pinealocytes, we show that rhythmic expression of\n                    <jats:italic>Bsx<\/jats:italic>\n                    is controlled at the transcriptional level by the sympathetic neural input to the gland acting via adrenergic stimulation with cyclic AMP as a second messenger. siRNA\u2010mediated knockdown (&gt;80% reduction) in pinealocyte cultures revealed\n                    <jats:italic>Bsx<\/jats:italic>\n                    to be a negative regulator of other pineal homeobox genes, including paired box 4 (\n                    <jats:italic>Pax4<\/jats:italic>\n                    ), but no effect on genes encoding melatonin\u2010synthesizing enzymes was detected. RNA sequencing analysis performed on siRNA\u2010treated pinealocytes further revealed that downstream target genes of\n                    <jats:italic>Bsx<\/jats:italic>\n                    are mainly involved in developmental processes. Thus, rhythmic\n                    <jats:italic>Bsx<\/jats:italic>\n                    expression seems to govern other developmental regulators in the mature pineal gland.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12629","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T05:15:43Z","timestamp":1575609343000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Circadian regulation and molecular role of the\n                    <i>Bsx<\/i>\n                    homeobox gene in the adult pineal gland"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4018-9242","authenticated-orcid":false,"given":"Mikkel B.","family":"Carstensen","sequence":"first","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-8983","authenticated-orcid":false,"given":"Henrik","family":"Hertz","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-4792","authenticated-orcid":false,"given":"Tenna","family":"Bering","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3263-7482","authenticated-orcid":false,"given":"Morten","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Rohde","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-5806","authenticated-orcid":false,"given":"David C.","family":"Klein","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5233-0277","authenticated-orcid":false,"given":"Steven L.","family":"Coon","sequence":"additional","affiliation":[{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-6324","authenticated-orcid":false,"given":"Martin F.","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,30]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R600036200"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-002-0580-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.137.7.8770929"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-012-0906-y"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1155"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-014-0740-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03773.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0882"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2011.07385.x"},{"key":"e_1_2_8_11_1","article-title":"The Lhx4 homeobox transcript in the rat 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