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. Author manuscript; available in PMC: 2024 Aug 26.
Published in final edited form as: Nat Rev Neurosci. 2010 Aug;11(8):563–576. doi: 10.1038/nrn2880

Figure 4: Transcriptional dominance model of photoreceptor cell fate determination.

Figure 4:

A generic photoreceptor is formed under the control of homeobox protein OTX2 and other undetermined signals. This precursor is programmed to possess a ‘default’ S cone state under the control of OTX2 (and/or cone–rod homeobox protein (CRX)) and nuclear receptor RORβ unless diverted into a rod or M cone state by additional signals. The ‘NRL control box’ determines whether a precursor becomes a rod or a cone, and the ‘thyroid hormone receptor β2 (TRβ2) control box’ prompts a cone to acquire an M opsin or an S opsin identity. Each control box is subject to modifying regulators. Induction of neural retina leucine zipper protein (NRL) and its target, photoreceptor-specific nuclear receptor (NR2E3), induces a rod state and suppresses cone genes, which consolidates the rod fate. Other factors involved in rod development include E3 SUMO-protein ligase PIAS3, neurogenic differentiation factor 1 (NEUROD1), achaete-scute homologue 1 (ASCL1; also known as MASH1), myocyte enhancer factor 2C and retinoblastoma-associated protein, probably at both early and later stages of differentiation. If NRL and NR2E3 fail to act, photoreceptor precursors follow the ‘default’ pathway to S cones unless TRβ2 and its ligand triiodothyronine (T3) induce M opsin and suppress S opsin expression in spatially restricted patterns in cone subpopulations over the retina. Other factors involved in M opsin and S opsin patterning include retinoid X receptor-γ (RXRγ), RORβ, RORα, COUP transcription factors (COUP-TFs) and CRX. NEUROD1 and bone morphogenetic protein receptor type 1A–1B contribute to inducing the expression of TRβ2 and COUP-TF, respectively.