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Open Access Highly Accessed Research article

Identification of two novel activities of the Wnt signaling regulator Dickkopf 3 and characterization of its expression in the mouse retina

Rei EI Nakamura12, Dale D Hunter3, Hyun Yi1, William J Brunken4 and Abigail S Hackam12*

Author affiliations

1 Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA

2 Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL, USA

3 Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA

4 Department of Anatomy and Cell Biology, State University of New York, Downstate Medical Center, Brooklyn, NY, USA

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Citation and License

BMC Cell Biology 2007, 8:52  doi:10.1186/1471-2121-8-52

Published: 19 December 2007

Abstract

Background

The Wnt signaling pathway is a cellular communication pathway that plays critical roles in development and disease. A major class of Wnt signaling regulators is the Dickkopf (Dkk) family of secreted glycoproteins. Although the biological properties of Dickkopf 1 (Dkk1) and Dickkopf 2 (Dkk2) are well characterized, little is known about the function of the related Dickkopf 3 (Dkk3) protein in vivo or in cell lines. We recently demonstrated that Dkk3 transcripts are upregulated during photoreceptor death in a mouse model of retinal degeneration. In this study, we characterized the activity of Dkk3 in Wnt signaling and cell death.

Results

Dkk3 was localized to Müller glia and retinal ganglion cells in developing and adult mouse retina. Western blotting confirmed that Dkk3 is secreted from Müller glia cells in culture. We demonstrated that Dkk3 potentiated Wnt signaling in Müller glia and HEK293 cells but not in COS7 cells, indicating that it is a cell-type specific regulator of Wnt signaling. This unique Dkk3 activity was blocked by co-expression of Dkk1. Additionally, Dkk3 displayed pro-survival properties by decreasing caspase activation and increasing viability in HEK293 cells exposed to staurosporine and H2O2. In contrast, Dkk3 did not protect COS7 cells from apoptosis.

Conclusion

These data demonstrate that Dkk3 is a positive regulator of Wnt signaling, in contrast to its family member Dkk1. Furthermore, Dkk3 protects against apoptosis by reducing caspase activity, suggesting that Dkk3 may play a cytoprotective role in the retina.