Making the Gradient: Thyroid Hormone Regulates Cone Opsin Expression in the Developing Mouse Retina

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 16; pp. 6218 - 6223
• Main Authors: Roberts, Melanie R., Srinivas, Maya, Forrest, Douglas, de Escobar, Gabriella Morreale, Reh, Thomas A.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.04.2006
• Subjects: Animals; Biological Sciences; Cone opsins; Gene expression; Hormone receptors; Hormones; Ligands; Mice; Mice, Transgenic; Opsins; Photoreceptors; Receptors; Retina; Retina - growth & development; Retina - metabolism; Retinal Cone Photoreceptor Cells - growth & development; Retinal Cone Photoreceptor Cells - metabolism; Rod Opsins - antagonists & inhibitors; Rod Opsins - genetics; Rod Opsins - metabolism; Rodents; Thyroid gland; Thyroid Hormone Receptors beta - genetics; Thyroid Hormone Receptors beta - metabolism; Thyroid Hormone Receptors beta - physiology; Thyroid Hormone Resistance Syndrome - genetics; Thyroid Hormone Resistance Syndrome - metabolism; Thyroid hormones; Transgenic animals; Triiodothyronine - metabolism; Triiodothyronine - pharmacology; Triiodothyronine - physiology; Wavelengths
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0509981103

Most mammals have two types of cone photoreceptors, which contain either medium wavelength (M) or short wavelength (S) opsin. The number and spatial organization of cone types varies dramatically among species, presumably to fine-tune the retina for different visual environments. In the mouse, S-and M-opsin are expressed in an opposing dorsal-ventral gradient. We previously reported that cone opsin patterning requires thyroid hormone β2, a nuclear hormone receptor that regulates transcription in conjunction with its ligand, thyroid hormone (TH). Here we show that exogenous TH inhibits S-opsin expression, but activates M-opsin expression. Binding of endogenous TH to TRPβ2 is required to inhibit S-opsin and to activate M-opsin. TH is symmetrically distributed in the retina at birth as S-opsin expression begins, but becomes elevated in the dorsal retina at the time of M-opsin onset (postnatal day 10). Our results show that TH is a critical regulator of both S-opsin and M-opsin, and suggest that a TH gradient may play a role in establishing the gradient of M-opsin. These results also suggest that the ratio and patterning of cone types may be determined by TH availability during retinal development.