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Cdo suppresses canonical Wnt signalling via interaction with Lrp6 thereby promoting neuronal differentiation

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  • Myong-Ho Jeong

    (Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute)

  • Seok-Man Ho

    (Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute)

  • Tuan Anh Vuong

    (Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute)

  • Shin-Bum Jo

    (Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute)

  • Guizhong Liu

    (Icahn School of Medicine at Mount Sinai)

  • Stuart A. Aaronson

    (Icahn School of Medicine at Mount Sinai)

  • Young-Eun Leem

    (Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute)

  • Jong-Sun Kang

    (Sungkyunkwan University School of Medicine, Samsung Biomedical Research Institute)

Abstract

Canonical Wnt signalling regulates expansion of neural progenitors and functions as a dorsalizing signal in the developing forebrain. In contrast, the multifunctional co-receptor Cdo promotes neuronal differentiation and is important for the function of the ventralizing signal, Shh. Here we show that Cdo negatively regulates Wnt signalling during neurogenesis. Wnt signalling is enhanced in Cdo-deficient cells, leading to impaired neuronal differentiation. The ectodomains of Cdo and Lrp6 interact via the Ig2 repeat of Cdo and the LDLR repeats of Lrp6, and the Cdo Ig2 repeat is necessary for Cdo-dependent Wnt inhibition. Furthermore, the Cdo-deficient dorsal forebrain displays stronger Wnt signalling activity, increased cell proliferation and enhanced expression of the dorsal markers and Wnt targets, Pax6, Gli3, Axin2. Therefore, in addition to promoting ventral central nervous system cell fates with Shh, Cdo promotes neuronal differentiation by suppression of Wnt signalling and provides a direct link between two major dorsoventral morphogenetic signalling pathways.

Suggested Citation

  • Myong-Ho Jeong & Seok-Man Ho & Tuan Anh Vuong & Shin-Bum Jo & Guizhong Liu & Stuart A. Aaronson & Young-Eun Leem & Jong-Sun Kang, 2014. "Cdo suppresses canonical Wnt signalling via interaction with Lrp6 thereby promoting neuronal differentiation," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6455
    DOI: 10.1038/ncomms6455
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