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Planar polarization of node cells determines the rotational axis of node cilia

Abstract

Rotational movement of the node cilia generates a leftward fluid flow in the mouse embryo1 because the cilia are posteriorly tilted2,3. However, it is not known how anterior-posterior information is translated into the posterior tilt of the node cilia. Here, we show that the basal body of node cilia is initially positioned centrally but then gradually shifts toward the posterior side of the node cells. Positioning of the basal body and unidirectional flow were found to be impaired in compound mutant mice lacking Dvl genes. Whereas the basal body was normally positioned in the node cells of Wnt3a−/− embryos, inhibition of Rac1, a component of the noncanonical Wnt signalling pathway, impaired the polarized localization of the basal body in wild-type embryos. Dvl2 and Dvl3 proteins were found to be localized to the apical side of the node cells, and their location was polarized to the posterior side of the cells before the posterior positioning of the basal body. These results suggest that posterior positioning of the basal body, which provides the posterior tilt to node cilia, is determined by planar polarization mediated by noncanonical Wnt signalling.

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Figure 1: Basal body position in node cells and nodal flow dynamics during development of the mouse embryo.
Figure 2: Time-lapse imaging of the basal body in the node.
Figure 3: Basal body position and nodal flow in Dvl mutant embryos.
Figure 4: Role of the noncanonical Wnt pathway in basal body positioning.
Figure 5: Polarized localization of Dvl2–EGFP and Dvl3–EYFP fusion proteins in node cells.

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Acknowledgements

We thank J. Gleeson (University of California, San Diego) for Centrin2–EGFP transgenic mice, K. Nakao (RIKEN, CDB) for KikGR mice, S. Piccolo (University of Padua) for BAT-gal, Y. Ikawa and S. Ohishi (Osaka University) for technical assistance and J. Axelrod and D. Antic (UCSF) for communicating their results on Prickle2 before publication. This work was supported by a grant from CREST (Core Research for Evolutional Science and Technology) of the Japan Science and Technology Corporation and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to H.H.) as well as grants from the National Institutes of Health (HD43173) and March of Dimes (to A.W.-B.).

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M.H. designed the study, performed most of the experiments, discussed the data and wrote the manuscript; K.S. analysed PIV data; S.I., S.Y., C.M. and S.N. contributed to the earlier phase of this work; J.W, S.T. and K.H. provided mice and discussed the data; A.W.-B. and H.H. discussed the data and wrote the manuscript.

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Correspondence to Anthony Wynshaw-Boris or Hiroshi Hamada.

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The authors declare no competing financial interests.

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Hashimoto, M., Shinohara, K., Wang, J. et al. Planar polarization of node cells determines the rotational axis of node cilia. Nat Cell Biol 12, 170–176 (2010). https://doi.org/10.1038/ncb2020

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