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The neurotrophin-receptor-related protein NRH1 is essential for convergent extension movements

Nature Cell Biology volume 6, pages 741–748 (2004)Cite this article

Abstract

Early spherical Xenopus laevis embryos are transformed into a streamlined shape through convergent extension movements. Here we report that a p75NTR-related transmembrane protein, NRH1, has an essential function in the regulation of these movements. NRH1 was expressed in marginal zone tissues of the gastrula and in the posterior ectoderm of the neurula. Attenuation of the NRH1 function inhibited convergent extension movements in the embryo and in activin-treated animal caps. NRH1 activated downstream effectors of the Wnt/planar cell polarity pathway: small GTPases and the cascade of MKK7–JNK. Furthermore, gain- and loss-of-function phenotypes of NRH1 were rescued by co-injection of dominant-negative and constitutively active forms of these downstream effectors, respectively, suggesting that NRH1 functions as a positive modulator of planar cell polarity signalling. Interestingly, NRH1 does not require Dishevelled (Xdsh) for the activation of these downstream effectors or translocation of Xdsh to the membrane, suggesting that NRH1 signalling interacts with planar cell polarity signalling downstream of Xdsh. This demonstrates an essential role for p75NTR-related signalling in early embryonic morphogenesis.

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Figure 1: Structure, expression and ligand-binding assays of a novel p75NTR-related protein.
Figure 2: Both gain- and loss-of-function phenotypes of NRH1 exhibit inhibition of convergent extension movements.
Figure 3: NRH1 activates small GTPases through a Frz7/Xdsh-independent pathway.
Figure 4: Activation of the Rac–MKK7–JNK pathway by NRH1 is independent of Xdsh.
Figure 5: NRH1 injection does not affect the subcellular localization of Xdsh.

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Acknowledgements

We are grateful to T. Hirano, T. Yokota and R. Nishinakamura for plasmids; H. Steinbeisser, M. Tada, T. Yamashita, M. Hibi, H. Enomoto and R. Ladher for their advice and comments on this work; H. Inomata for discussion and M. Matsumura for technical assistance. This work was supported by grants to Y.S. from MEXT, the Kobe Cluster Project and the Leading Project.

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  1. Organogenesis and Neurogenesis Group, Center for Developmental Biology, RIKEN 2-2-3 Minatojima-minamimachi, Chuo Kobe, 650-0047, Japan

    Noriaki Sasai, Yoko Nakazawa, Tomoko Haraguchi & Yoshiki Sasai

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  1. Noriaki Sasai
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Correspondence to Yoshiki Sasai.

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Sasai, N., Nakazawa, Y., Haraguchi, T. et al. The neurotrophin-receptor-related protein NRH1 is essential for convergent extension movements. Nat Cell Biol 6, 741–748 (2004). https://doi.org/10.1038/ncb1158

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