Feedback induction of a photoreceptor-specific isoform of retinoid-related orphan nuclear receptor {beta} by the rod transcription factor NRL [Neurobiology]

October 8th, 2014 by Fu, Y., Liu, H., Ng, L., Kim, J.-w., Hao, H., Swaroop, A., Forrest, D.

Vision requires the generation of cone and rod photoreceptors that function in daylight and dim light, respectively. The NRL transcription factor critically controls photoreceptor fates as it stimulates rod differentiation and suppresses cone differentiation. However, the controls over NRL induction that balance rod and cone fates remain unclear. We reported previously that the retinoid-related orphan receptor β gene (Rorb) is required for Nrl expression and other retinal functions. We show that Rorb differentially expresses two isoforms: RORβ2 in photoreceptors and RORβ1 in photoreceptors, progenitor cells and other cell types. Deletion of RORβ2 or RORβ1 increased the cone:rod ratio ~2-fold whereas deletion of both isoforms in Rorb-/- mice produced almost exclusively cone-like cells at the expense of rods, suggesting that both isoforms induce Nrl. Electroporation of either RORβ isoform into retinal explants from Rorb-/- neonates re-activated Nrl and rod genes but in Nrl-/- explants failed to re-activate rod genes, indicating that NRL is the effector for both RORβ isoforms in rod differentiation. Unexpectedly, RORβ2 expression was lost in Nrl-/- mice. Moreover, NRL activated the RORβ2-specific promoter of Rorb indicating that NRL activates Rorb, its own inducer gene. We suggest that feedback activation between Nrl and Rorb genes reinforces commitment to rod differentiation.
  • Posted in Journal of Biological Chemistry, Publications
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