Feedback induction of a photoreceptor-specific isoform of retinoid-related orphan nuclear receptor ? by the rod transcription factor NRL.

ABSTRACT: Vision requires the generation of cone and rod photoreceptors that function in daylight and dim light, respectively. The neural retina leucine zipper factor (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 have reported previously that the retinoid-related orphan receptor ? gene (Rorb) is required for Nrl expression and other retinal functions. We show that Rorb differentially expresses two isoforms: ROR?2 in photoreceptors and ROR?1 in photoreceptors, progenitor cells, and other cell types. Deletion of ROR?2 or ROR?1 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 ROR? isoform into retinal explants from Rorb(-/-) neonates reactivated Nrl and rod genes but, in Nrl(-/-) explants, failed to reactivate rod genes, indicating that NRL is the effector for both ROR? isoforms in rod differentiation. Unexpectedly, ROR?2 expression was lost in Nrl(-/-) mice. Moreover, NRL activated the ROR?2-specific promoter of Rorb, indicating that NRL activates Rorb, its own inducer gene. We suggest that feedback activation between Nrl and Rorb genes reinforces the commitment to rod differentiation.

SUBMITTER: Fu Y 

PROVIDER: S-EPMC4239602 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature