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Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation

Nature volume 430, pages 689–693 (2004)Cite this article

Abstract

Oriented cell division is an integral part of pattern development in processes ranging from asymmetric segregation of cell-fate determinants to the shaping of tissues1,2. Despite proposals that it has an important function in tissue elongation3,4, the mechanisms regulating division orientation have been little studied outside of the invertebrates Caenorhabditis elegans and Drosophila melanogaster1. Here, we have analysed mitotic divisions during zebrafish gastrulation using in vivo confocal imaging and found that cells in dorsal tissues preferentially divide along the animal–vegetal axis of the embryo. Establishment of this animal–vegetal polarity requires the Wnt pathway components Silberblick/Wnt11, Dishevelled and Strabismus. Our findings demonstrate an important role for non-canonical Wnt signalling in oriented cell division during zebrafish gastrulation, and indicate that oriented cell division is a driving force for axis elongation. Furthermore, we propose that non-canonical Wnt signalling has a conserved role in vertebrate axis elongation, orienting both cell intercalation and mitotic division.

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Figure 1: Imaging analysis of division orientation in zebrafish gastrula.
Figure 2: Relationship between cell elongation and division orientations.
Figure 3: Components of the PCP pathway regulate division orientation.
Figure 4: Contribution of oriented cell division to axis elongation.

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References

  1. Ahringer, J. Control of cell polarity and mitotic spindle positioning in animal cells. Curr. Opin. Cell Biol. 15, 73–81 (2003)

    Article  CAS  Google Scholar 

  2. Sausedo, R. A., Smith, J. L. & Schoenwolf, G. C. Role of nonrandomly oriented cell division in shaping and bending of the neural plate. J. Comp. Neurol. 381, 473–488 (1997)

    Article  CAS  Google Scholar 

  3. Schoenwolf, G. C. & Alvarez, I. S. Roles of neuroepithelial cell rearrangement and division in shaping of the avian neural plate. Development 106, 427–439 (1989)

    CAS  PubMed  Google Scholar 

  4. Wei, Y. & Mikawa, T. Formation of the avian primitive streak from spatially restricted blastoderm: evidence for polarized cell division in the elongating streak. Development 127, 87–96 (2000)

    CAS  PubMed  Google Scholar 

  5. Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B. & Schilling, T. F. Stages of embryonic development of the zebrafish. Dev. Dyn. 203, 253–310 (1995)

    Article  CAS  Google Scholar 

  6. Kimmel, C. B., Warga, R. M. & Kane, D. A. Cell cycles and clonal strings during formation of the zebrafish central nervous system. Development 120, 265–276 (1994)

    CAS  PubMed  Google Scholar 

  7. Woo, K. & Fraser, S. E. Order and coherence in the fate map of the zebrafish nervous system. Development 121, 2595–2609 (1995)

    CAS  Google Scholar 

  8. Concha, M. L. & Adams, R. J. Oriented cell divisions and cellular morphogenesis in the zebrafish gastrula and neurula: a time-lapse analysis. Development 125, 983–994 (1998)

    CAS  PubMed  Google Scholar 

  9. Hertwig, O. Ueber den Werth der ersten Furchungszellen fur die Organbildung des Embryo. Experimentelle Studien am Froschund Tritonei. Arch. Mikrosk. Anat. 42, 662–804 (1893)

    Article  Google Scholar 

  10. Black, S. D. & Vincent, J. P. The first cleavage plane and the embryonic axis are determined by separate mechanisms in Xenopus laevis. II. Experimental dissociation by lateral compression of the egg. Dev. Biol. 128, 65–71 (1988)

    Article  CAS  Google Scholar 

  11. Wallingford, J. B. et al. Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405, 81–85 (2000)

    Article  ADS  CAS  Google Scholar 

  12. Tada, M. & Smith, J. C. Xwnt11 is a target of Xenopus Brachyury: regulation of gastrulation movements via Dishevelled, but not through the canonical Wnt pathway. Development 127, 2227–2238 (2000)

    CAS  Google Scholar 

  13. Jessen, J. R. et al. Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. Nature Cell Biol. 4, 610–615 (2002)

    Article  CAS  Google Scholar 

  14. Rothbacher, U. et al. Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. EMBO J. 19, 1010–1022 (2000)

    Article  CAS  Google Scholar 

  15. Hashimoto, H. et al. Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation. Dev. Biol. 217, 138–152 (2000)

    Article  CAS  Google Scholar 

  16. Tago, K. et al. Inhibition of Wnt signaling by ICAT, a novel β-catenin-interacting protein. Genes Dev. 14, 1741–1749 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  17. He, X., Semenov, M., Kamai, K. & Zeng, X. LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signalling: Arrows point the way. Development 131, 1663–1677 (2004)

    Article  CAS  Google Scholar 

  18. Heisenberg, C. P. et al. Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405, 76–81 (2000)

    Article  ADS  CAS  Google Scholar 

  19. Kilian, B. et al. The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech. Dev. 120, 467–476 (2003)

    Article  CAS  Google Scholar 

  20. Moon, R. T. et al. Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis. Development 119, 97–111 (1993)

    CAS  Google Scholar 

  21. Park, M. & Moon, R. T. The planar cell-polarity gene stbm regulates cell behaviour and cell fate in vertebrate embryos. Nature Cell Biol. 4, 20–25 (2002)

    Article  CAS  Google Scholar 

  22. Glickman, N. S., Kimmel, C. B., Jones, M. A. & Adams, R. J. Shaping the zebrafish notochord. Development 130, 873–887 (2003)

    Article  CAS  Google Scholar 

  23. Elul, T. & Keller, R. Monopolar protrusive activity: a new morphogenic cell behavior in the neural plate dependent on vertical interactions with the mesoderm in Xenopus. Dev. Biol. 224, 3–19 (2000)

    Article  CAS  Google Scholar 

  24. Sausedo, R. A. & Schoenwolf, G. C. Quantitative analyses of cell behaviors underlying notochord formation and extension in mouse embryos. Anat. Rec. 239, 103–112 (1994)

    Article  CAS  Google Scholar 

  25. Schlesinger, A., Shelton, C. A., Maloof, J. N., Meneghini, M. & Bowerman, B. Wnt pathway components orient a mitotic spindle in the early Caenorhabditis elegans embryo without requiring gene transcription in the responding cell. Genes Dev. 13, 2028–2038 (1999)

    Article  CAS  Google Scholar 

  26. Gho, M. & Schweisguth, F. Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature 393, 178–181 (1998)

    Article  ADS  CAS  Google Scholar 

  27. Chalmers, A. D., Strauss, B. & Papalopulu, N. Oriented cell divisions asymmetrically segregate aPKC and generate cell fate diversity in the early Xenopus embryo. Development 130, 2657–2668 (2003)

    Article  CAS  Google Scholar 

  28. Das, T., Payer, B., Cayouette, M. & Harris, W. A. In vivo time-lapse imaging of cell divisions during neurogenesis in the developing zebrafish retina. Neuron 37, 597–609 (2003)

    Article  CAS  Google Scholar 

  29. Koster, R. W. & Fraser, S. E. Tracing transgene expression in living zebrafish embryos. Dev. Biol. 233, 329–346 (2001)

    Article  CAS  Google Scholar 

  30. Campbell, R. E. et al. A monomeric red fluorescent protein. Proc. Natl Acad. Sci. USA 99, 7877–7882 (2002)

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Hibi (Zdkk1), M. Park (Stbm MO), J. Wallingford (Xdsh-D2), R. Köster (H2B–GFP), S. Megason (H2B–RFP1 and membrane RFP1), M. Tada (Xdsh-ΔPDZ and Xdsh-DEP + ) and H. McBride (ICAT) for providing the plasmids and morpholino, and C.-P. Heisenberg for the silberblick/wnt11 mutants. We also thank S. Bhattacharyya, M. Bronner-Fraser, M. Garcia-Castro, D. Koos, R. Köster, B. Link, S. Megason and J. Wallingford for discussion and critical reading of the manuscript.

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Authors and Affiliations

  1. Biological Imaging Center, Beckman Institute, California Institute of Technology, Pasadena, California, 91125, USA

    Ying Gong & Scott E. Fraser

  2. Biochemistry and Molecular Biophysics, Division of Biology, California Institute of Technology, Pasadena, California, 91125, USA

    Ying Gong, Chunhui Mo & Scott E. Fraser

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  1. Ying Gong
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Correspondence to Scott E. Fraser.

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Supplementary information

Supplementary Figure 1

This figure shows the details of the Xdd1 mosaic experiment. The time-lapse images show examples of mis-oriented divisions of mosaic Xdd1-expressing cells among wild-type cells that divide normally, indicating that Dsh controls cell division orientation cell autonomously. Divisions of these mosaic Xdd1 cells are plotted in the line graphs. (PDF 1160 kb)

Supplementary Figure 1 Legend (DOC 21 kb)

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Gong, Y., Mo, C. & Fraser, S. Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation. Nature 430, 689–693 (2004). https://doi.org/10.1038/nature02796

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