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Expression of Notch and Wnt pathway components and activation of Notch signaling in medulloblastomas from heterozygous patched mice

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Summary

Hedgehog (Hh), Notch, and Wingless (Wnt) signaling control normal development of the cerebellum, and dysregulation of these signaling pathways are associated with medulloblastoma (MB). As an initial step in the study of the role of interacting signaling pathways in MB pathogenesis, we demonstrate the expression of several components of the Notch and Wnt signaling pathways, and activation of Notch signaling in MB from Ptch +/− mice that have elevated Hh signaling. We also show a marked downregulation in the expression of Notch2, Jagged1, Hes1, mSfrp1, and mFrz7 in cerebella of developing mice with reduced Hh signaling, suggesting that Hh signaling regulates the expression of these genes. Together with recent published data, these findings indicate that Hh signaling might synergize simultaneously with Notch and Wnt signaling in MB development by controlling Notch and Wnt pathway ligand, receptor and/or target gene expression.

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Acknowledgements

We thank A. P. McMahon for kindly providing us with Nestin Cre;Smo n/c mice. This work was supported by funding from the National Cancer Institute of Canada and the Canadian Institutes of Health Research to VAW who is also the recipient of a CIHR New Investigator Award. G. D. Dakubo was a recipient of an M. S. Society Postdoctoral Fellowship at the time that these experiments were performed.

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  1. Gabriel D. Dakubo

    Present address: Genesis Genomics Inc., 310-1294 Balmoral St., P7B 5Z5, Thunder Bay, ON, Canada

Authors and Affiliations

  1. Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, K1H 8L6, Ottawa, ON, Canada

    Gabriel D. Dakubo, Chantal J. Mazerolle & Valerie A. Wallace

  2. Eye Institute, University of Ottawa, 451 Smyth Road, K1H 8M5, Ottawa, ON, Canada

    Gabriel D. Dakubo, Chantal J. Mazerolle & Valerie A. Wallace

  3. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, K1H 8M5, Ottawa, ON, Canada

    Valerie A. Wallace

  4. Genesis Genomics Inc., 310-1294 Balmoral St., P7B 5Z5, Thunder Bay, ON, Canada

    Gabriel D. Dakubo

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  1. Gabriel D. Dakubo
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Correspondence to Gabriel D. Dakubo.

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Dakubo, G.D., Mazerolle, C.J. & Wallace, V.A. Expression of Notch and Wnt pathway components and activation of Notch signaling in medulloblastomas from heterozygous patched mice. J Neurooncol 79, 221–227 (2006). https://doi.org/10.1007/s11060-006-9132-2

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  • DOI: https://doi.org/10.1007/s11060-006-9132-2

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