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

Myong Ho Jeong; Seok Man Ho; Tuan Anh Vuong; Shin Bum Jo; Guizhong Liu; Stuart A. Aaronson; Young Eun Leem; Jong Sun Kang

doi:10.1038/ncomms6455

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

Myong Ho Jeong, Seok Man Ho, Tuan Anh Vuong, Shin Bum Jo, Guizhong Liu, Stuart A. Aaronson, Young Eun Leem, Jong Sun Kang

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34 Scopus citations

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.

Original language	English
Article number	5455
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6455
State	Published - 2014

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@article{49b7ab5738a0437c946b8327c02483fb,

title = "Cdo suppresses canonical Wnt signalling via interaction with Lrp6 thereby promoting neuronal differentiation",

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.",

author = "Jeong, {Myong Ho} and Ho, {Seok Man} and Vuong, {Tuan Anh} and Jo, {Shin Bum} and Guizhong Liu and Aaronson, {Stuart A.} and Leem, {Young Eun} and Kang, {Jong Sun}",

note = "Funding Information: We thank Drs R.S. Krauss and R. Simon for critical reading of the manuscript. We also thank Drs F. Costantini and B. Allen for providing plasmids. This work was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP; NRF-2011-0017315) and (NRF-2013M3A9B1069776).",

year = "2014",

doi = "10.1038/ncomms6455",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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T1 - Cdo suppresses canonical Wnt signalling via interaction with Lrp6 thereby promoting neuronal differentiation

AU - Jeong, Myong Ho

AU - Ho, Seok Man

AU - Vuong, Tuan Anh

AU - Jo, Shin Bum

AU - Liu, Guizhong

AU - Aaronson, Stuart A.

AU - Leem, Young Eun

AU - Kang, Jong Sun

N1 - Funding Information: We thank Drs R.S. Krauss and R. Simon for critical reading of the manuscript. We also thank Drs F. Costantini and B. Allen for providing plasmids. This work was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP; NRF-2011-0017315) and (NRF-2013M3A9B1069776).

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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DO - 10.1038/ncomms6455

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SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

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

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