No abstract

Color vision is supported by retinal cone photoreceptors that, in most mammals, express two photopigments sensitive to short (S‐opsin) or middle (M‐opsin) wavelengths. Expression of the Opn1sw and Opn1mw genes, encoding S‐opsin and M‐opsin, respectively, is under the control of nuclear receptors, including thyroid hormone receptor β2 (TRβ2), retinoid X receptor γ (RXRγ), and RORβ, a member of the retinoic acid receptor‐related orphan receptor (ROR) family. We now demonstrate that RORα, another member of the ROR family, regulates Opn1sw, Opn1mw, as well as Arr3 (cone arrestin) in the mouse retina. RORα expression is detected in cones by postnatal day 3 and maintained through adulthood. The retinas of staggerer mice, carrying a null mutation of RORα, show significant down‐regulation of Opn1sw, Opn1mw, and Arr3. RORα acts in synergy with cone‐rod homeobox transcription factor (Crx), to activate the Opn1sw promoter in vitro. Chromatin immunoprecipitation assays reveal that RORα directly binds to the Opn1sw promoter, Opn1mw locus control region, and the Arr3 promoter in vivo. Our data suggest that RORα plays a crucial role in cone development by directly regulating multiple cone genes.

A weak, nonselective G protein-coupled receptor 120 (GPR120) agonist 10 was found by screening a series of carboxylic acids derived from the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist 3. Modification based on the homology model of GPR120 led to the first GPR120-selective agonist 12. These results provide a basis for constructing new tools for probing the biology of GPR120 and for developing new candidate therapeutic agents.