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RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice

Oncogene volume 30, pages 313–322 (2011)Cite this article

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Abstract

The Notch signaling pathway is an ubiquitous cell–cell interaction mechanism, which is essential in controlling processes like cell proliferation, cell fate decision, differentiation or stem cell maintenance. Recent data have shown that Notch signaling is RBP-Jκ-dependent in melanocytes, being required for survival of these pigment cells that are responsible for coloration of the skin and hairs in mammals. In addition, Notch is believed to function as an oncogene in melanoma, whereas it is a tumor suppressor in mouse epidermis. In this study, we addressed the implication of the Notch signaling in the development of another population of pigment cells forming the retinal pigment epithelium (RPE) in mammalian eyes. The constitutive activity of Notch in Tyrp1::NotchIC/° transgenic mice enhanced RPE cell proliferation, and the resulting RPE-derived pigmented tumor severely affected the overall eye structure. This RPE cell proliferation is dependent on the presence of the transcription factor RBP-Jκ, as it is rescued in mice lacking RBP-Jκ in the RPE. In conclusion, Notch signaling in the RPE uses the canonical pathway, which is dependent on the transcription factor RBP-Jκ. In addition, it is of importance for RPE development, and constitutive Notch activity leads to hyperproliferation and benign tumors of these pigment cells.

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Acknowledgements

We thank Pierre Chambon, Tatsuko Honjo, Ursula Zimber-Strobl, Lothar Strobl and Ian J Jackson for mouse strains; to Simon Saule, Vince Hearing and Mickey Marks for antibodies; and to Alessandra Solero and Sabrina Guichard for initial help with the Tyrp1::NotchIC construct and mice. The Pax6 antibody developed by A Kawakami was obtained from the Developmental Studies Hybridoma Bank at the University of Iowa. Work in the laboratory of FB was supported by grants from Oncosuisse, Novartis, the Fondation Emma Muschamps and The Swiss National Science Foundation.

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  1. Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, (EPFL), Lausanne, Switzerland

    K Schouwey, I T Aydin, F Radtke & F Beermann

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Schouwey, K., Aydin, I., Radtke, F. et al. RBP-Jκ-dependent Notch signaling enhances retinal pigment epithelial cell proliferation in transgenic mice. Oncogene 30, 313–322 (2011). https://doi.org/10.1038/onc.2010.428

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