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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References
Nonaka, S. et al. Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829–837 (1998).
Nonaka, S. et al. De novo formation of left-right asymmetry by posterior tilt of nodal cilia. PLoS biol. 3, e268 (2005).
Okada, Y., Takeda, S., Tanaka, Y., Belmonte, J. C. & Hirokawa, N. Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination. Cell 121, 633–644 (2005).
Hirokawa, N., Tanaka, Y., Okada, Y. & Takeda, S. Nodal flow and the generation of left-right asymmetry. Cell 125, 33–45 (2006).
Shiratori, H. & Hamada, H. The left-right axis in the mouse: from origin to morphology. Development 133, 2095–2104 (2006).
Blum, M., Weber, T., Beyer, T. & Vick, P. Evolution of leftward flow. Semin. Cell Dev. Biol. (2008).
Gros, J., Feistel, K., Viebahn, C., Blum, M. & Tabin, C. J. Cell movements at Hensen's node establish left/right asymmetric gene expression in the chick. Science 324, 941–944 (2009).
Marshall, W. F. & Kintner, C. Cilia orientation and the fluid mechanics of development. Curr. Opin. Cell Biol. 20, 48–52 (2008).
Maisonneuve, C. et al. Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow. Development 136, 3019–3030 (2009).
Raffel, M., Willert, C. & Kompenhans, J. Particle Image Velocimetry: A Practical Guide. (Springer, 1998).
Shinohara, K. et al. High-speed micro-PIV measurement of transient flow in microfluidic devices. Meas. Sci. Technol. 15, 1965–1970 (2004).
Lee, J. D. & Anderson, K. V. Morphogenesis of the node and notochord: the cellular basis for the establishment and maintenance of left-right asymmetry in the mouse. Dev. Dyn. 237, 3464–3476 (2008).
Higginbotham, H., Bielas, S., Tanaka, T. & Gleeson, J. G. Transgenic mouse line with green-fluorescent protein-labeled Centrin 2 allows visualization of the centrosome in living cells. Transgenic Res. 13, 155–164 (2004).
Kurotaki, Y., Hatta, K., Nakao, K., Nabeshima, Y. & Fujimori, T. Blastocyst axis is specified independently of early cell lineage but aligns with the ZP shape. Science 316, 719–723 (2007).
Etheridge, S. L. et al. Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development. PLoS Genet. 4, e1000259 (2008).
Nakamura, T. et al. Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system. Dev. Cell 11, 495–504 (2006).
Maretto, S. et al. Mapping Wnt/β-catenin signaling during mouse development and in colorectal tumors. Proc. Natl Acad. Sci. USA 100, 3299–3304 (2003).
Nakaya, M. A. et al. Wnt3a links left-right determination with segmentation and anteroposterior axis elongation. Development 132, 5425–5436 (2005).
Karner, C., Wharton, K. A., Jr. & Carroll, T. J. Planar cell polarity and vertebrate organogenesis. Semin. Cell Dev. Biol. 17, 194–203 (2006).
Zallen, J. A. Planar polarity and tissue morphogenesis. Cell 129, 1051–1063 (2007).
Wang, J. et al. Regulation of polarized extension and planar cell polarity in the cochlea by the vertebrate PCP pathway. Nature Genet. 37, 980–985 (2005).
Kispert, A., Vainio, S., Shen, L., Rowitch, D. H. & McMahon, A. P. Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips. Development 122, 3627–3637 (1996).
Yamaguchi, T. P., Bradley, A., McMahon, A. P. & Jones, S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126, 1211–1223 (1999).
Majumdar, A., Vainio, S., Kispert, A., McMahon, J. & McMahon, A. P. Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 130, 3175–3185 (2003).
Lijam, N. et al. Social interaction and sensorimotor gating abnormalities in mice lacking Dvl1. Cell 90, 895–905 (1997).
Hamblet, N. S. et al. Dishevelled 2 is essential for cardiac outflow tract development, somite segmentation and neural tube closure. Development 129, 5827–5838 (2002).
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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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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DOI: https://doi.org/10.1038/ncb2020
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