Making the gradient: Thyroid hormone regulates cone opsin expression in the developing mouse retina

doi:10.1073/pnas.0509981103

Making the gradient: Thyroid hormone regulates cone opsin expression in the developing mouse retina

*Graduate Program in Neurobiology and Behavior and Department of Biological Structure, University of Washington, Box 357420, Seattle, WA 98195-7420;
^†Department of Human Genetics, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029;
^‡National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892; and
^§Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Cientificas and Universidad Autonóma de Madrid, Arturo Duperier 4, 28029 Madrid, Spain

Edited by Jeremy Nathans, Johns Hopkins University School of Medicine, Baltimore, MD, and approved March 1, 2006 (received for review November 17, 2005)

Abstract

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 TRβ2 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.

Footnotes

^¶To whom correspondence should be addressed. E-mail: tomreh{at}u.washington.edu
Author contributions: M.R.R., M.S., D.F., G.M.d.E., and T.A.R. designed research; M.R.R., M.S., G.M.d.E., and T.A.R. performed research; M.R.R., M.S., G.M.d.E., and T.A.R. analyzed data; and M.R.R. and T.A.R. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

Abbreviations:

TH,

thyroid hormone;

RXR,

retinoid X receptor;

TRβ2,

TH β2 receptor isoform;

S-opsin,

short wavelength opsin;

M-opsin,

medium wavelength opsin;

Pn,

postnatal day n.