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A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis

Nature volume 446, pages 797–800 (2007)Cite this article

Abstract

The development of cell polarity is an essential prerequisite for tissue morphogenesis during embryogenesis, particularly in the development of epithelia1,2. In addition, oriented cell division can have a powerful influence on tissue morphogenesis3. Here we identify a novel mode of polarized cell division that generates pairs of neural progenitors with mirror-symmetric polarity in the developing zebrafish neural tube and has dramatic consequences for the organization of embryonic tissue. We show that during neural rod formation the polarity protein Pard3 is localized to the cleavage furrow of dividing progenitors, and then mirror-symmetrically inherited by the two daughter cells. This allows the daughter cells to integrate into opposite sides of the developing neural tube. Furthermore, these mirror-symmetric divisions have powerful morphogenetic influence: when forced to occur in ectopic locations during neurulation, they orchestrate the development of mirror-image pattern formation and the consequent generation of ectopic neural tubes.

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Figure 1: Cell division separates daughter cells across the midline of the neural keel and rod.
Figure 2: Subcellular distribution of Pard3–GFP reveals that C-division is a mirror-symmetric division.
Figure 3: Delayed convergence of the neural plate leads to ectopic Pard3-mediated C-divisions.
Figure 4: Delayed neural plate convergence generates duplicate neural tubes complete with mirror-image apico-basal polarity and ventricles.

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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  Google Scholar 

  2. Wodarz, A. Establishing cell polarity in development. Nature Cell Biol. 4, 39–44 (2002)

    Article  Google Scholar 

  3. Gong, Y., Mo, C. & Fraser, S. E. Planar cell polarity signalling controls cell division orientation during zebrafish gastrulation. Nature 430, 689–693 (2004)

    Article  ADS  CAS  Google Scholar 

  4. Papan, C. & Campos-Ortega, J. A. A clonal analysis of spinal cord development in the zebrafish. Dev. Genes Evol. 207, 71–81 (1997)

    Article  Google Scholar 

  5. Papan, C. & Campos-Ortega, J. A. Region-specific cell clones in the developing spinal cord of the zebrafish. Dev. Genes Evol. 209, 135–144 (1999)

    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. Ciruna, B., Jenny, A., Lee, D., Mlodzik, M. & Schier, A. F. Planar cell polarity signalling couples cell division and morphogenesis during neurulation. Nature 439, 220–224 (2006)

    Article  ADS  CAS  Google Scholar 

  8. Lowery, L. A. & Sive, H. Initial formation of zebrafish brain ventricles occurs independently of circulation and requires the nagie oko and snakehead/atp1a1a. 1 gene products. Development 132, 2057–2067 (2005)

    Article  CAS  Google Scholar 

  9. Geldmacher-Voss, B., Reugels, A. M., Pauls, S. & Campos-Ortega, J. A. A 90° rotation of the mitotic spindle changes the orientation of mitoses of zebrafish neuroepithelial cells. Development 130, 3767–3780 (2003)

    Article  CAS  Google Scholar 

  10. Lyons, D. A., Guy, A. T. & Clarke, J. D. Monitoring neural progenitor fate through multiple rounds of division in an intact vertebrate brain. Development 130, 3427–3436 (2003)

    Article  CAS  Google Scholar 

  11. Macara, I. G. Parsing the polarity code. Nature Rev. Mol. Cell Biol. 5, 220–231 (2004)

    Article  CAS  Google Scholar 

  12. Wei, X. et al. The zebrafish Pard3 ortholog is required for separation of the eye fields and retinal lamination. Dev. Biol. 269, 286–301 (2004)

    Article  CAS  Google Scholar 

  13. Von Trotha, J. W., Campos-Ortega, J. A. & Reugels, A. M. Apical localization of ASIP/PAR-3:EGFP in zebrafish neuroepithelial cells involves the oligomerization domain CR1, the PDZ domains, and the C-terminal portion of the protein. Dev. Dyn. 235, 967–977 (2006)

    Article  CAS  Google Scholar 

  14. 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 

  15. 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 

  16. 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  Google Scholar 

  17. Carreira-Barbosa, F. et al. Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish. Development 130, 4037–4046 (2003)

    Article  CAS  Google Scholar 

  18. Wallingford, J. B. & Harland, R. M. Neural tube closure requires Dishevelled-dependent convergent extension of the midline. Development 129, 5815–5825 (2002)

    Article  CAS  Google Scholar 

  19. 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 

  20. Bakkers, J. et al. Has2 is required upstream of Rac1 to govern dorsal migration of lateral cells during zebrafish gastrulation. Development 131, 525–537 (2004)

    Article  CAS  Google Scholar 

  21. Lyons, D. A. et al. erbb3 and erbb2 are essential for Schwann cell migration and myelination in zebrafish. Curr. Biol. 15, 513–524 (2005)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We would like to thank P. Alexandre, D. Barker, J. Brockes, M. Costa, M. Kai, R. Sousa-Nunes, V. Prince and S. Wilson for comments and discussion on the manuscript; M. Costa for Supplementary Movie 1; S. Goulas for Fig. 4c, f; and M. Hammerschmidt for the has2 morpholino. This work was funded by the MRC, the BBSRC and the Wellcome Trust.

Author Contributions M. Tawk and C.A. contributed most of the experimental data. D.A.L., G.C.G and P.R.B. contributed additional experimental data. A.M.R. provided the pard3–GFP and pard3-Δ6–GFP constructs. D.R.H. provided Pard3 antisera and initial Pard3 morpholino. M. Tada provided constructs and helped design experiments. J.D.W.C conceived the project, designed experiments and wrote the manuscript together with M.Tawk.

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Author notes

  1. Dave A. Lyons & Philippa R. Bayley

    Present address: Present addresses: Department of Developmental Biology, Stanford University School of Medicine, Beckman Center B300, 279 Campus Drive, Stanford, California 94305, USA (D.A.L.); Department of Academic and Student Affairs, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA (P.R.B).,

Authors and Affiliations

  1. Anatomy and Developmental Biology, UCL, Gower Street, London WC1E 6BT, UK,

    Marcel Tawk, Claudio Araya, Dave A. Lyons, Gemma C. Girdler, Philippa R. Bayley, Masazumi Tada & Jonathan D. W. Clarke

  2. Institut für Entwicklungsbiologie, Universität zu Köln, 50923 Köln, Germany,

    Alexander M. Reugels

  3. Department of Biological Sciences and Center for Zebrafish Research, University of Notre Dame, Notre Dame, Indiana 46556, USA,

    David R. Hyde

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Correspondence to Jonathan D. W. Clarke.

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Supplementary information

Supplementary Information

This file contains Supplementary Figures1-9 with Legends, Supplementary Methods, Supplementary Table 1, Supplementary Movies 1-5 Legends and additional references (PDF 983 kb)

Supplementary Movie 1

This file contains Supplementary Movie 1 which shows single confocal plane at level of the hindbrain in a wild-type embryo. Cells labelled with membrane GFP and imaged at 5 minute intervals. Outlines of neural plate, neural keel and neural rod are intermittently shown with dotted lines. Otic vesicle (ov) lies to right of neural rod at end of movie. (MOV 1399 kb)

Supplementary Movie 2

This file contains Supplementary Movie 2 which shows single confocal plane at level of the caudal hindbrain in a trilobite/vangl2 mutant embryo. Cells labelled with membrane GFP and imaged at 5 minute intervals. Outline of neural plate and resultant 4 layered neural rod are shown with dotted lines. Note emergence of double epithelial phenotype towards end of movie. (MOV 1710 kb)

Supplementary Movie 3

This file contains Supplementary Movie 3 which shows single confocal plane of neural keel cell in a trilobite/vangl2 mutant embryo. Cell labelled with Pard3-GFP and imaged at 5 minute intervals. Bright expression of Pard3-GFP is first observed at telophase on either side of the cleavage plane and is then mirror-symmetrically expressed in the two daughter cells before cleavage is completed. Cell outlines dotted at start and end of sequence. (MOV 92 kb)

Supplementary Movie 4

This file contains Supplementary Movie 4 which shows single confocal plane of neural keel cell in a trilobite/vangl2 mutant embryo. Cell labelled with Pard3-GFP and imaged at 5 minute intervals. Bright expression of Pard3-GFP is first concentrated close to the cleavage plane at telophase and is then mirror-symmetrically expressed in the two daughter cells before cleavage is completed. Cell outlines dotted at start and end of sequence. (MOV 57 kb)

Supplementary Movie 5

This file contains Supplementary Movie 5 which shows single confocal plane at level of the anterior spinal cord in an embryo injected with has2 morpholino. Cells labelled with membrane GFP and imaged at 5 minute intervals. Outlines of neural plate, neural keel and resultant 4 layered neural rod are shown intermittently with dotted lines. Note emergence of double epithelial phenotype towards end of movie. (MOV 633 kb)

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Tawk, M., Araya, C., Lyons, D. et al. A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis. Nature 446, 797–800 (2007). https://doi.org/10.1038/nature05722

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