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This Article Free via Open Access: OA OA Full Text Full Text (PDF) Supplemental Data OA All Versions of this Article: 2007-0900v1 2007-0900v2 26/8/2063    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Denayer, T. Articles by Vleminckx, K. Search for Related Content PubMed PubMed Citation Articles by Denayer, T. Articles by Vleminckx, K.

TISSUE-SPECIFIC STEM CELLS

Canonical Wnt Signaling Controls Proliferation of Retinal Stem/Progenitor Cells in Postembryonic Xenopus Eyes

^aDepartment of Molecular Biomedical Research, VIB, Ghent, Belgium;
^bDepartment of Molecular Biology, Ghent University, Ghent, Belgium;
^cUMR CNRS 8080, Université Paris Sud, Orsay, France;
^dInstitute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany

Key Words. Canonical Wnt pathway • Retina • Ciliary marginal zone • Stem cell • Proliferation • Xenopus laevis

Correspondence: Correspondence: Kris Vleminckx, Ph.D., Technologiepark 927, B-9052 Ghent, Belgium. Telephone: 32-9-33-13-720; Fax: 32-9-33-13-609; e-mail: Kris.Vleminckx{at}dmbr.ugent.be; or Muriel Perron, Ph.D., Université Paris Sud, UMR CNRS 8080, Orsay, France. Telephone: 331-69-15-72-25; Fax: 331-69-15-68-02; e-mail: muriel.perron{at}u-psud.fr

Received on October 30, 2007; accepted for publication on May 5, 2008.

First published online in STEM CELLS EXPRESS  June 12, 2008.

Vertebrate retinal stem cells, which reside quiescently within the ciliary margin, may offer a possibility for treatment of degenerative retinopathies. The highly proliferative retinal precursor cells in Xenopus eyes are confined to the most peripheral region, called the ciliary marginal zone (CMZ). Although the canonical Wnt pathway has been implicated in the developing retina of different species, little is known about its involvement in postembryonic retinas. Using a green fluorescent protein-based Wnt-responsive reporter, we show that in transgenic Xenopus tadpoles, the canonical Wnt signaling is activated in the postembryonic CMZ. To further investigate the functional implications of this, we generated transgenic, hormone-inducible canonical Wnt pathway activating and repressing systems, which are directed to specifically intersect at the nuclear endpoint of transcriptional Wnt target gene activation. We found that postembryonic induction of the canonical Wnt pathway in transgenic retinas resulted in increased proliferation in the CMZ compartment. This is most likely due to delayed cell cycle exit, as inferred from a pulse-chase experiment on 5-bromo-2'-deoxyuridine-labeled retinal precursors. Conversely, repression of the canonical Wnt pathway inhibited proliferation of CMZ cells. Neither activation nor repression of the Wnt pathway affected the differentiated cells in the central retina. We conclude that even at postembryonic stages, the canonical Wnt signaling pathway continues to have a major function in promoting proliferation and maintaining retinal stem cells. These findings may contribute to the eventual design of vertebrate, stem cell-based retinal therapies.

Disclosure of potential conflicts of interest is found at the end of this article.