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Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning

Abstract

Remodelling its shape, or morphogenesis, is a fundamental property of living tissue. It underlies much of embryonic development and numerous pathologies. Convergent extension (CE) of the axial mesoderm of vertebrates is an intensively studied model for morphogenetic processes that rely on cell rearrangement. It involves the intercalation of polarized cells perpendicular to the antero-posterior (AP) axis, which narrows and lengthens the tissue1,2. Several genes have been identified that regulate cell behaviour underlying CE in zebrafish and Xenopus. Many of these are homologues of genes that control epithelial planar cell polarity in Drosophila1,2,3,4,5. However, elongation of axial mesoderm must be also coordinated with the pattern of AP tissue specification to generate a normal larval morphology. At present, the long-range control that orients CE with respect to embryonic axes is not understood. Here we show that the chordamesoderm of Xenopus possesses an intrinsic AP polarity that is necessary for CE, functions in parallel to Wnt/planar cell polarity signalling, and determines the direction of tissue elongation. The mechanism that establishes AP polarity involves graded activin-like signalling and directly links mesoderm AP patterning to CE.

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Figure 1: AP polarity and chordamesoderm explant elongation.
Figure 2: Activin-induced elongation.
Figure 3: Convergent extension and Wnt/PCP signalling.

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References

  1. Keller, R. Shaping the vertebrate body plan by polarized embryonic cell movements. Science 298, 1950–1954 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Wallingford, J. B., Fraser, S. E. & Harland, R. M. Convergent extension: the molecular control of polarized cell movement during embryonic development. Dev. Cell 2, 695–706 (2002)

    Article  CAS  PubMed  Google Scholar 

  3. Mlodzik, M. Planar cell polarization: do the same mechanisms regulate Drosophila tissue polarity and vertebrate gastrulation? Trends Genet. 18, 564–571 (2002)

    Article  CAS  PubMed  Google Scholar 

  4. 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  PubMed  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  6. Smith, J. C., Price, B. M., Green, J. B., Weigel, D. & Herrmann, B. G. Expression of a Xenopus homolog of Brachyury (T) is an immediate–early response to mesoderm induction. Cell 67, 79–87 (1991)

    Article  CAS  PubMed  Google Scholar 

  7. Sasai, Y. et al. Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. Cell 79, 779–790 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Keller, R. & Danilchik, M. Regional expression, pattern and timing of convergence and extension during gastrulation of Xenopus laevis. Development 103, 193–209 (1988)

    CAS  PubMed  Google Scholar 

  9. Klein, P. S. & Melton, D. A. A molecular mechanism for the effect of lithium on development. Proc. Natl Acad. Sci. USA 93, 8455–8459 (1996)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sokol, S. & Melton, D. A. Pre-existent pattern in Xenopus animal pole cells revealed by induction with activin. Nature 351, 409–411 (1991)

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Ninomiya, H., Takahashi, S., Tanegashima, K., Yokota, C. & Asashima, M. Endoderm differentiation and inductive effect of activin-treated ectoderm in Xenopus. Dev. Growth Differ. 41, 391–400 (1999)

    Article  CAS  PubMed  Google Scholar 

  12. McDowell, N., Zorn, A. M., Crease, D. J. & Gurdon, J. B. Activin has direct long-range signalling activity and can form a concentration gradient by diffusion. Curr. Biol. 7, 671–681 (1997)

    Article  CAS  PubMed  Google Scholar 

  13. Green, J. B., New, H. B. & Smith, J. C. Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell 71, 731–739 (1992)

    Article  CAS  PubMed  Google Scholar 

  14. Gurdon, J. B., Harger, P., Mitchell, A. & Lemaire, P. Activin signalling and response to a morphogen gradient. Nature 371, 487–492 (1994)

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Gurdon, J. B. et al. Single cells can sense their position in a morphogen gradient. Development 126, 5309–5317 (1999)

    CAS  PubMed  Google Scholar 

  16. Thisse, B., Wright, C. V. E. & Thisse, C. Activin- and nodal-related factors control antero-posterior patterning of the zebrafish embryo. Nature 403, 425–428 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Gritsman, K., Talbot, W. S. & Schier, A. F. Nodal signaling patterns the organizer. Development 127, 921–932 (2000)

    CAS  PubMed  Google Scholar 

  18. Branford, W. W. & Yost, H. J. Lefty-dependent inhibition of Nodal- and Wnt-responsive organizer gene expression is essential for normal gastrulation. Curr. Biol. 12, 2136–2141 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. Irvine, K. D. & Wieschaus, E. Cell intercalation during Drosophila germband extension and its regulation by pair-rule segmentation genes. Development 120, 827–841 (1994)

    CAS  PubMed  Google Scholar 

  20. Zallen, J. A. & Wieschaus, E. Patterned gene expression directs bipolar planar polarity in Drosophila. Dev. Cell 6, 343–355 (2004)

    Article  CAS  PubMed  Google Scholar 

  21. Sokol, S. Y., Klingensmith, J., Perrimon, N. & Itoh, K. Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled. Development 121, 1637–1647 (1995)

    CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  24. Townes, P. L. & Holtfreter, J. Directed movements and selective adhesion of embryonic amphibian cells. J. Exp. Zool. 128, 53–120 (1955)

    Article  Google Scholar 

  25. Kinoshita, N., Iioka, H., Miyakoshi, A. & Ueno, N. PKCδ is essential for Dishevelled function in a noncanonical Wnt pathway that regulates Xenopus convergent extension movements. Genes Dev. 17, 1663–1676 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Goto, T. & Keller, R. The planar cell polarity gene strabismus regulates convergence and extension and neural fold closure in Xenopus. Dev. Biol. 247, 165–181 (2002)

    Article  CAS  PubMed  Google Scholar 

  27. 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  PubMed  Google Scholar 

  28. Strutt, D. Frizzled signalling and cell polarisation in Drosophila and vertebrates. Development 130, 4501–4513 (2003)

    Article  CAS  PubMed  Google Scholar 

  29. Smith, J. C. & Watt, F. M. Biochemical specificity of Xenopus notochord. Differentiation 29, 109–115 (1985)

    Article  CAS  PubMed  Google Scholar 

  30. Gwantka, V., Ellinger-Ziegelbauer, H. & Hausen, P. β1-Integrin is a maternal protein that is inserted into all newly formed plasma membranes during early Xenopus embryogenesis. Development 115, 595–605 (1992)

    Google Scholar 

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Acknowledgements

We thank the National Hormone & Pituitary Program and A. F. Parlow for recombinant human activin A; F. Watt for MZ15 antibody; P. Hausen for 8C8 antibody; E. M. DeRobertis, R. Harland and J. Smith for plasmids; Y. Masui and the members of the Elinson and Winklbauer laboratories for help and encouragement; and M. Makowiecki for manuscript suggestions. This work was supported by an International Collaborative Grant from the Human Frontier Science Program Organization to R.P.E. and by grants from the Natural Sciences and Engineering Research Council of Canada, the Canadian Institutes of Health Research, and the Canada Foundation for Innovation to R.W.

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Correspondence to Rudolf Winklbauer.

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The authors declare that they have no competing financial interests.

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Includes information on embryological manipulations and immunohistochemistry and in situ hybridization. (DOC 30 kb)

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Ninomiya, H., Elinson, R. & Winklbauer, R. Antero-posterior tissue polarity links mesoderm convergent extension to axial patterning. Nature 430, 364–367 (2004). https://doi.org/10.1038/nature02620

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