In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development

Neuroscience Graduate Program, Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA.
Human Molecular Genetics (Impact Factor: 6.39). 10/2006; 15(17):2588-602. DOI: 10.1093/hmg/ddl185
Source: PubMed


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.

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    Full-text · Article · Mar 2014 · PLoS ONE
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    • "photoreceptors through the activation of an orphan nuclear receptor Nr2e3 ( Cheng et al . , 2006 ) . Deletion of Nrl resulted in the loss of rod photoreceptors and Nr2e3 expression in the mutant retinas ( Mears et al . , 2001 ) . Nr2e3 was shown to activate rod - specific genes , but works in con - cert with CrX , represses cone - specific genes ( Cheng et al . , 2006 ; Chen et al . , 2005 ; Peng et al . , 2005 ) . Hori - zontal cell specification is regulated by the core group of Foxn4 , Ptf1a and Prox1 . In the absence of any of these three genes , horizontal cell genesis is impaired ( Dyer et al . , 2003 ; Li et al . , 2004 ; Fujitani et al . , 2006 ) . Hes1 and Hes5 , which is a negative regulato"
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