title: Nuclear receptor Rev-erb alpha (Nr1d1) functions in concert with Nr2e3 to regulate transcriptional networks in the retina.
abstract: The majority of diseases in the retina are caused by genetic mutations affecting the development and function of photoreceptor cells. The transcriptional networks directing these processes are regulated by genes such as nuclear hormone receptors. The nuclear hormone receptor gene Rev-erb alpha/Nr1d1 has been widely studied for its role in the circadian cycle and cell metabolism, however its role in the retina is unknown. In order to understand the role of Rev-erb alpha/Nr1d1 in the retina, we evaluated the effects of loss of Nr1d1 to the developing retina and its co-regulation with the photoreceptor-specific nuclear receptor gene Nr2e3 in the developing and mature retina. Knock-down of Nr1d1 expression in the developing retina results in pan-retinal spotting and reduced retinal function by electroretinogram. Our studies show that NR1D1 protein is co-expressed with NR2E3 in the outer neuroblastic layer of the developing mouse retina. In the adult retina, NR1D1 is expressed in the ganglion cell layer and is co-expressed with NR2E3 in the outer nuclear layer, within rods and cones. Several genes co-targeted by NR2E3 and NR1D1 were identified that include: Nr2c1, Recoverin, Rgr, Rarres2, Pde8a, and Nupr1. We examined the cyclic expression of Nr1d1 and Nr2e3 over a twenty-four hour period and observed that both nuclear receptors cycle in a similar manner. Taken together, these studies reveal a novel role for Nr1d1, in conjunction with its cofactor Nr2e3, in regulating transcriptional networks critical for photoreceptor development and function.
authors.affiliation: Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Nissa J
authors.initials: NJ
authors.lastname: Mollema
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Austin S
authors.initials: AS
authors.lastname: Jelcick
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sachs
authors.forename: Désirée
authors.initials: D
authors.lastname: von Alpen
authors.forename: Daniel
authors.initials: D
authors.lastname: Schorderet
authors.forename: Pascal
authors.initials: P
authors.lastname: Escher
authors.forename: Neena B
authors.initials: NB
authors.lastname: Haider
mesh_terms: D000375:Aging / Q000378:metabolism / Q000528:radiation effects; D000818:Animals; D002452:Cell Count; D004742:Enhancer Elements, Genetic / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics*; D007267:Injections; D008027:Light; D055537:Light Signal Transduction / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000378:metabolism*; D009928:Organ Specificity / Q000528:radiation effects; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D021381:Protein Transport / Q000528:radiation effects; D034741:RNA, Small Interfering / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000528:radiation effects; D013194:Staining and Labeling; D015533:Transcriptional Activation / Q000235:genetics / Q000528:radiation effects
chemical_list: C498262:Nr1d1 protein, mouse; C485736:Nr2e3 protein, mouse; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057093:Orphan Nuclear Receptors; D034741:RNA, Small Interfering