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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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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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