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.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Ahringer, J. Control of cell polarity and mitotic spindle positioning in animal cells. Curr. Opin. Cell Biol. 15, 73–81 (2003)
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)
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)
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)
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)
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)
Woo, K. & Fraser, S. E. Order and coherence in the fate map of the zebrafish nervous system. Development 121, 2595–2609 (1995)
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)
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)
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)
Wallingford, J. B. et al. Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405, 81–85 (2000)
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)
Jessen, J. R. et al. Zebrafish trilobite identifies new roles for Strabismus in gastrulation and neuronal movements. Nature Cell Biol. 4, 610–615 (2002)
Rothbacher, U. et al. Dishevelled phosphorylation, subcellular localization and multimerization regulate its role in early embryogenesis. EMBO J. 19, 1010–1022 (2000)
Hashimoto, H. et al. Zebrafish Dkk1 functions in forebrain specification and axial mesendoderm formation. Dev. Biol. 217, 138–152 (2000)
Tago, K. et al. Inhibition of Wnt signaling by ICAT, a novel β-catenin-interacting protein. Genes Dev. 14, 1741–1749 (2000)
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)
Heisenberg, C. P. et al. Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405, 76–81 (2000)
Kilian, B. et al. The role of Ppt/Wnt5 in regulating cell shape and movement during zebrafish gastrulation. Mech. Dev. 120, 467–476 (2003)
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)
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)
Glickman, N. S., Kimmel, C. B., Jones, M. A. & Adams, R. J. Shaping the zebrafish notochord. Development 130, 873–887 (2003)
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)
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)
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)
Gho, M. & Schweisguth, F. Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature 393, 178–181 (1998)
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)
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)
Koster, R. W. & Fraser, S. E. Tracing transgene expression in living zebrafish embryos. Dev. Biol. 233, 329–346 (2001)
Campbell, R. E. et al. A monomeric red fluorescent protein. Proc. Natl Acad. Sci. USA 99, 7877–7882 (2002)
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.
The authors declare that they have no competing financial interests.
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)
About this article
Cell Reports (2019)
The Journal of Cell Biology (2019)
Epithelial geometry regulates spindle orientation and progenitor fate during formation of the mammalian epidermis
Current Opinion in Genetics & Development (2018)
Pediatric Cardiology (2018)