TY - JOUR
T1 - Activation of the blue opsin gene in cone photoreceptor development by retinoid-related orphan receptor β
AU - Srinivas, Maya
AU - Ng, Lily
AU - Liu, Hong
AU - Jia, Li
AU - Forrest, Douglas
PY - 2006
Y1 - 2006
N2 - Color vision requires the expression of opsin photopigments with different wavelength sensitivities in retinal cone photoreceptors. The basic color visual system of mammals is dichromatic, involving differential expression in the cone population of two opsins with sensitivity to short (S, blue) or medium (M, green) wavelengths. However, little is known of the factors that directly activate these opsin genes and thereby contribute to the S or M opsin identity of the cone. We report that the orphan nuclear receptor RORβ (retinoid-related orphan receptor β) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. RORβ lacks a known physiological ligand and activates the Opn1sw promoter modestly alone but strongly in synergy with the retinal cone-rod homeobox factor (CRX), suggesting a cooperative means of enhancing RORβ activity. Comparison of wild-type and mutant lacZ reporter transgenes showed that the RORβ-binding sites in Opn1sw are required for expression in mouse retina. RORβ-deficient mice fail to induce S opsin appropriately during postnatal cone development. Photoreceptors in these mice also lack outer segments, indicating additional functions for RORβ in photoreceptor morphological maturation. The results identify Opn1sw as a target gene for RORβ and suggest a key role for RORβ in regulating opsin expression in the color visual system.
AB - Color vision requires the expression of opsin photopigments with different wavelength sensitivities in retinal cone photoreceptors. The basic color visual system of mammals is dichromatic, involving differential expression in the cone population of two opsins with sensitivity to short (S, blue) or medium (M, green) wavelengths. However, little is known of the factors that directly activate these opsin genes and thereby contribute to the S or M opsin identity of the cone. We report that the orphan nuclear receptor RORβ (retinoid-related orphan receptor β) activates the S opsin gene (Opn1sw) through binding sites upstream of the gene. RORβ lacks a known physiological ligand and activates the Opn1sw promoter modestly alone but strongly in synergy with the retinal cone-rod homeobox factor (CRX), suggesting a cooperative means of enhancing RORβ activity. Comparison of wild-type and mutant lacZ reporter transgenes showed that the RORβ-binding sites in Opn1sw are required for expression in mouse retina. RORβ-deficient mice fail to induce S opsin appropriately during postnatal cone development. Photoreceptors in these mice also lack outer segments, indicating additional functions for RORβ in photoreceptor morphological maturation. The results identify Opn1sw as a target gene for RORβ and suggest a key role for RORβ in regulating opsin expression in the color visual system.
UR - http://www.scopus.com/inward/record.url?scp=33746585709&partnerID=8YFLogxK
U2 - 10.1210/me.2005-0505
DO - 10.1210/me.2005-0505
M3 - Article
C2 - 16574740
AN - SCOPUS:33746585709
SN - 0888-8809
VL - 20
SP - 1728
EP - 1741
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 8
ER -