Distinct functions of photoreceptor cell-specific nuclear receptor, thyroid hormone receptor beta2 and CRX in one photoreceptor development.
OBJECTIVE
To clarify the functions of a specific subtype of thyroid hormone receptor (TR), TRbeta2, and photoreceptor cell-specific nuclear receptor (PNR) in the development of cone photoreceptors.


METHODS
The expression of short (S)- and medium (M)-wavelength cone opsins was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis in mice without a functional PNR (rd7/rd7 mice), and levels of plasma thyroid hormones and expression of TRbeta2 were also examined. Concomitantly, by means of reporter assays, the roles of PNR and TRbeta2 in the S- and M-cone opsin expression were explored at the transcriptional level.


RESULTS
In rd7/rd7 mice, an abnormal increase in cone photoreceptors was observed immediately before retinal maturation normally occurs. Although an increase in S-cone opsin in the retina was observed during and after retinal development, the expression of M-cone opsin expression was not perturbed during retinal maturation. Plasma concentrations of thyroid hormone and levels of TRbeta2 expression in the rd7/rd7 mouse retina over the developmental period were normal. Transcriptional studies demonstrated that TRbeta2, but not PNR, activated the M-cone opsin gene promoter function, while suppressing the S-cone opsin promoter function enhanced by CRX in a thyroid hormone-dependent manner.


CONCLUSIONS
The results indicate that PNR may suppress proliferation of cone photoreceptor progenitor cells and that the regulation of S- and M-cone opsin gene expression is mediated by TRbeta2 and CRX, but not by PNR. Thus, our results partly disclosed the molecular mechanism of cone photoreceptor development, highlighting the distinct functions of PNR and TRbeta2.
Yanagi
Yasuo
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan. yanagi-tky@umin.ac.jp
Takezawa
Shin-Ichiro
S
Kato
Shigeaki
S
D000818:Animals; D015152:Blotting, Northern; D018398:Homeodomain Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D057093:Orphan Nuclear Receptors; D012313:RNA / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000196:embryology* / Q000378:metabolism; D012162:Retinal Degeneration / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000502:physiology*; D013963:Thyroid Hormones / Q000097:blood; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection
D018398:Homeodomain Proteins; C485736:Nr2e3 protein, mouse; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D017299:Rod Opsins; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D015534:Trans-Activators; D014157:Transcription Factors; C109288:cone rod homeobox protein; D012313:RNA