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In the pineal gland, a brain structure devoted to nocturnal melatonin synthesis, a number of homeobox genes are also expressed postnatally; among these is the LIM homeobox 4 gene (\n                    <jats:italic>Lhx4<\/jats:italic>\n                    ). We here report that\n                    <jats:italic>Lhx4<\/jats:italic>\n                    is specifically expressed in the postnatal pineal gland of rats and humans. Circadian analyses revealed a fourfold rhythm in\n                    <jats:italic>Lhx4<\/jats:italic>\n                    expression in the rat pineal gland, with rhythmic expression detectable from postnatal day 10. Pineal\n                    <jats:italic>Lhx4<\/jats:italic>\n                    expression was confirmed to be positively driven by adrenergic signaling, as evidenced by in vivo modulation of\n                    <jats:italic>Lhx4<\/jats:italic>\n                    expression by pharmacological (isoprenaline injection) and surgical (superior cervical ganglionectomy) interventions. In cultured pinealocytes,\n                    <jats:italic>Lhx4<\/jats:italic>\n                    expression was upregulated by cyclic AMP, a second messenger of norepinephrine. By use of RNAscope technology,\n                    <jats:italic>Lhx4<\/jats:italic>\n                    transcripts were found to be exclusively localized in melatonin\u2010synthesizing pinealocytes. This prompted us to investigate the possible role of\n                    <jats:italic>Lhx4<\/jats:italic>\n                    in regulation of melatonin\u2010producing enzymes. By use of siRNA technology, we knocked down\n                    <jats:italic>Lhx4<\/jats:italic>\n                    by 95% in cultured pinealocytes; this caused a reduction in transcripts encoding the melatonin\u2010producing enzyme arylalkylamine N\u2010acetyl transferase (\n                    <jats:italic>Aanat<\/jats:italic>\n                    ). Screening the transcriptome of siRNA\u2010treated pinealocytes by RNAseq revealed a significant impact of\n                    <jats:italic>Lhx4<\/jats:italic>\n                    on the phototransduction pathway and on transcripts involved in development of the nervous system and photoreceptors. These data suggest that rhythmic expression of\n                    <jats:italic>Lhx4<\/jats:italic>\n                    in the pineal gland is controlled via an adrenergic\u2010cyclic AMP mechanism and that\n                    <jats:italic>Lhx4<\/jats:italic>\n                    acts to promote nocturnal melatonin synthesis.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12616","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T06:51:29Z","timestamp":1571035889000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The\n                    <i>Lhx4<\/i>\n                    homeobox transcript in the rat pineal gland: Adrenergic regulation and impact on transcripts encoding melatonin\u2010synthesizing enzymes"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4600-8983","authenticated-orcid":false,"given":"Henrik","family":"Hertz","sequence":"first","affiliation":[{"name":"Department of Neuroscience Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel B.","family":"Carstensen","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"}]},{"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\/0000-0002-3263-7482","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":"Agnete M.","family":"Granau","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\/0000-0002-5233-0277","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\/0000-0002-1792-5806","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\/0000-0002-4047-6324","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 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