Expression of photoreceptor-specific nuclear receptor NR2E3 in rod photoreceptors of fetal human retina.
OBJECTIVE
To study the physiological function of NR2E3 and possible molecular mechanisms underlying enhanced short-wavelength cone syndrome (ESCS) pathogenesis in developing human retina, and to compare its expression to that of Neural Retina Leucine zipper (NRL), a transcription factor essential for rod differentiation.


METHODS
Expression of NR2E3, a photoreceptor-specific orphan nuclear receptor, was examined in human retinas between fetal weeks (Fwk) 9 to 22 by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Both NR2E3 and NRL expression patterns were followed by immunocytochemistry. The human retina develops in a central to peripheral pattern, in which a protein may take weeks to be expressed throughout the entire retina. This allowed a detailed temporal analysis of NR2E3 and NRL expression.


RESULTS
NR2E3 expression was detected shortly after the appearance of NRL in putative immature rods on the foveal edge at Fwk 11.7. Expression of both markers was maintained in rod opsin expressing fetal photoreceptors. NR2E3 expression was not detected in either long/medium- or short-wavelength cones. Its absence from cones was also supported by the position of labeled nuclei deep in the outer nuclear layer, and by the absence of NR2E3 from the fovea.


CONCLUSIONS
A role for NR2E3 in the rod developmental pathway is suggested. The closely related expression patterns of NRL and NR2E3 supported an interactive function, where both transcription factors determine the rod fate and suppress immature rods from adopting the S-cone fate.
Bumsted O'Brien
Keely M
KM
Max Planck Institute for Brain Research, Neuroanatomy Department, Frankfurt am Main, Germany. k.bumsted@auckland.ac.nz
Cheng
Hong
H
Jiang
Yibin
Y
Schulte
Dorothea
D
Swaroop
Anand
A
Hendrickson
Anita E
AE
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D018613:Microscopy, Confocal; D057093:Orphan Nuclear Receptors; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D012160:Retina / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005136:Eye Proteins; C403073:NR2E3 protein, human; C490037:NRL protein, human; C485736:Nr2e3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors