title: Retinoic Acid Signaling Regulates Differential Expression of the Tandemly-Duplicated Long Wavelength-Sensitive Cone Opsin Genes in Zebrafish.
abstract: The signaling molecule retinoic acid (RA) regulates rod and cone photoreceptor fate, differentiation, and survival. Here we elucidate the role of RA in differential regulation of the tandemly-duplicated long wavelength-sensitive (LWS) cone opsin genes. Zebrafish embryos were treated with RA from 48 hours post-fertilization (hpf) to 75 hpf, and RNA was isolated from eyes for microarray analysis. ~170 genes showed significantly altered expression, including several transcription factors and components of cellular signaling pathways. Of interest, the LWS1 opsin gene was strongly upregulated by RA. LWS1 is the upstream member of the tandemly duplicated LWS opsin array and is normally not expressed embryonically. Embryos treated with RA 48 hpf to 100 hpf or beyond showed significant reductions in LWS2-expressing cones in favor of LWS1-expressing cones. The LWS reporter line, LWS-PAC(H) provided evidence that individual LWS cones switched from LWS2 to LWS1 expression in response to RA. The RA signaling reporter line, RARE:YFP indicated that increased RA signaling in cones was associated with this opsin switch, and experimental reduction of RA signaling in larvae at the normal time of onset of LWS1 expression significantly inhibited LWS1 expression. A role for endogenous RA signaling in regulating differential expression of the LWS genes in postmitotic cones was further supported by the presence of an RA signaling domain in ventral retina of juvenile zebrafish that coincided with a ventral zone of LWS1 expression. This is the first evidence that an extracellular signal may regulate differential expression of opsin genes in a tandemly duplicated array.
authors: Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America.
authors: Diana M
authors: DM
authors: Mitchell
authors: Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America.
authors: Craig B
authors: CB
authors: Stevens
authors: Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America.
authors: Ruth A
authors: RA
authors: Frey
authors: Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America; Bioinformatics and Computational Biology Graduate Program, University of Idaho, Moscow, Idaho, United States of America.
authors: Samuel S
authors: SS
authors: Hunter
authors: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
authors: Ryuichi
authors: R
authors: Ashino
authors: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
authors: Shoji
authors: S
authors: Kawamura
authors: Department of Biological Sciences, University of Idaho, Moscow, Idaho, United States of America; Bioinformatics and Computational Biology Graduate Program, University of Idaho, Moscow, Idaho, United States of America; Neuroscience Graduate Program, University of Idaho, Moscow, Idaho, United States of America.
authors: Deborah L
authors: DL
authors: Stenkamp
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D055358:Cone Opsins / Q000235:genetics* / Q000378:metabolism; D005123:Eye / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055355:Opsins / Q000235:genetics* / Q000378:metabolism; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D015534:Trans-Activators; D059467:Transcriptome; D014212:Tretinoin / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D055358:Cone Opsins; C000607384:Opn1lw1 protein, zebrafish; D055355:Opsins; D015534:Trans-Activators; D029961:Zebrafish Proteins; C516569:cxxc1b protein, zebrafish; D014212:Tretinoin