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Pias3-dependent SUMOylation controls mammalian cone photoreceptor differentiation

Nature Neuroscience volume 13, pages 1059–1065 (2010)Cite this article

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Abstract

Selective expression of retinal cone opsin genes is essential for color vision, but the mechanism mediating this process is poorly understood. Both vertebrate rod and medium wavelength–sensitive (M) cone photoreceptors differentiate by repression of a short wavelength–sensitive (S) cone differentiation program. We found that Pias3 acts in mouse cone photoreceptors to activate expression of M opsin and repress expression of S opsin, with the transcription factors Trβ2 and Rxrγ mediating preferential expression of Pias3 in M cones. Finally, we observed that Pias3 directly regulated M and S cone opsin expression by modulating the cone-enriched transcription factors Rxrγ, Rorα and Trβ1. Our results indicate that Pias3-dependent SUMOylation of photoreceptor-specific transcription factors is a common mechanism that controls both rod and cone photoreceptor subtype specification, regulating distinct molecular targets in the two cell types.

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Figure 1: Pias3 is preferentially expressed in cones expressing M cone opsin.
Figure 2: Pias3-dependent SUMOylation is necessary and sufficient to direct cone opsin subtype expression.
Figure 3: Pias3 is a transcriptional target of Trβ2 and Rxrγ.
Figure 4: T3-regulated cone photoreceptor subtype specification is Pias3 dependent.
Figure 5: Pias3-dependent regulation of cone subtype specification can occur independently of Trβ2.
Figure 6: Molecular mechanism of action of Pias3 in developing cones.

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Acknowledgements

We thank D. Forrest for providing antibodies to Trβ2 and for supplying Trβ2−/− and Trβ1−/−; Trβ2−/− mice. We also thank J. Nathans, T. Shimogori, W. Yap and members of the Blackshaw laboratory for their comments on the manuscript. This work was supported by grants from the US National Institutes of Health (R01EY017015 to S.B. and RO1EY012543 to S.C.). S.B. is a W.M. Keck Distinguished Young Investigator in Medical Science.

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Author notes

  1. Akishi Onishi

    Present address: Present address: Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka, USA.,

Authors and Affiliations

  1. Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Akishi Onishi & Seth Blackshaw

  2. Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, USA

    Guang-Hua Peng & Shiming Chen

  3. Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA

    Shiming Chen

  4. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Seth Blackshaw

  5. Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Seth Blackshaw

  6. Center for High-Throughput Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Seth Blackshaw

  7. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Seth Blackshaw

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Contributions

A.O., S.C. and S.B. designed the study. A.O. and G.-H.P. performed the experiments. A.O., G.-H.P. and S.C. contributed reagents and analytic tools. A.O., G.-H.P., S.C. and S.B. analyzed the data. A.O. and S.B. wrote the manuscript.

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Correspondence to Seth Blackshaw.

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Onishi, A., Peng, GH., Chen, S. et al. Pias3-dependent SUMOylation controls mammalian cone photoreceptor differentiation. Nat Neurosci 13, 1059–1065 (2010). https://doi.org/10.1038/nn.2618

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