| First Author | Cheng H | Year | 2006 |
| Journal | Hum Mol Genet | Volume | 15 |
| Issue | 17 | Pages | 2588-602 |
| PubMed ID | 16868010 | Mgi Jnum | J:114905 |
| Mgi Id | MGI:3690386 | Doi | 10.1093/hmg/ddl185 |
| Citation | Cheng H, et al. (2006) In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development. Hum Mol Genet 15(17):2588-602 |
| abstractText | Rod and cone photoreceptors in mammalian retina are generated from common pool(s) of neuroepithelial progenitors. NRL, CRX and NR2E3 are key transcriptional regulators that control photoreceptor differentiation. Mutations in NR2E3, a rod-specific orphan nuclear receptor, lead to loss of rods, increased density of S-cones and supernormal S-cone-mediated vision in humans. To better understand its in vivo function, NR2E3 was expressed ectopically in the Nrl-/- retina, where post-mitotic precursors fated to be rods develop into functional S-cones similar to the human NR2E3 disease. Expression of NR2E3 in the Nrl-/- retina completely suppressed cone differentiation and resulted in morphologically rod-like photoreceptors, which were however not functional. Gene profiling of FACS-purified photoreceptors confirmed the role of NR2E3 as a strong suppressor of cone genes but an activator of only a subset of rod genes (including rhodopsin) in vivo. Ectopic expression of NR2E3 in cone precursors and differentiating S-cones of wild-type retina also generated rod-like cells. The dual regulatory function of NR2E3 was not dependent upon the presence of NRL and/or CRX, but on the timing and level of its expression. Our studies reveal a critical role of NR2E3 in establishing functional specificity of NRL-expressing photoreceptor precursors during retinal neurogenesis. |
