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Cadherin-dependent filopodia control preimplantation embryo compaction

Nature Cell Biology volume 15, pages 14241433 (2013) | Download Citation

Abstract

Compaction of the preimplantation embryo is the earliest morphogenetic process essential for mammalian development, yet it remains unclear how round cells elongate to form a compacted embryo. Here, using live mouse embryo imaging, we demonstrate that cells extend long E-cadherin-dependent filopodia on to neighbouring cells, which control the cell shape changes necessary for compaction. We found that filopodia extension is tightly coordinated with cell elongation, whereas retraction occurs before cells become round again before dividing. Laser-based ablations revealed that filopodia are required to maintain elongated cell shapes. Moreover, molecular disruption of the filopodia components E-cadherin, α- and β-catenin, F-actin and myosin-X prevents cells from elongating and compacting the embryo. Finally, we show that early filopodia formation triggered by overexpressing myosin-X is sufficient to induce premature compaction. Our findings establish a role for filopodia during preimplantation embryonic development and provide an in vivo context to investigate the biological functions of filopodia in mammals.

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Acknowledgements

We thank A. Yap, E. Jesudason, A. Fouras and J. Polo for comments on the manuscript; T. Bell for advice on laser ablations; S. Firth and I. Harper for help with imaging experiments; and R. Cheney, A. Yap and B. Henderson for sharing DNA constructs. N.P. is supported by ARC DP120104594 and DE120100794, NHMRC APP1052171 and Monash University Strategic and Interdisciplinary grants, and J.C.F-G. by Wenner-Gren Foundations and Swedish Society for Medical Research Postdoctoral Fellowships.

Author information

Author notes

    • Juan Carlos Fierro-González
    •  & Melanie D. White

    These authors contributed equally to this work

Affiliations

  1. European Molecular Biology Laboratory, Australian Regenerative Medicine Institute, Level 1 Building 75, Monash University, Victoria 3800, Australia

    • Juan Carlos Fierro-González
    • , Melanie D. White
    • , Juan Carlos Silva
    •  & Nicolas Plachta

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Contributions

J.C.F-G. and M.D.W. designed and performed the experiments. J.C.S. performed embryo microinjections and manipulations. N.P. supervised the project. J.C.F-G., M.D.W. and N.P. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Nicolas Plachta.

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    Supplementary Information

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Videos

  1. 1.

    Filopodia dynamics during mouse embryo compaction.

    Time-lapse imaging of a representative embryo during compaction shows two cells extending filopodia, which then fully retract before cell division. The embryo was microinjected with memb-mCherry into one cell at the 2-cell stage. Orthogonal scale bar, 5 μm.

  2. 2.

    E-cad-labelled filopodia retract to the filopodia-forming cell.

    Time-lapse imaging of a representative embryo during compaction shows a cell (left) with E-cad-GFP-expressing filopodia extended onto its E-cad-GFP-labelled neighbouring cell (right). The long finger-like processes clearly retract and return to the membrane apical border region where filopodia initially attached (left). Orthogonal scale bar, 5 μm.

  3. 3.

    Filopodia retraction occurs before cell division.

    Time-lapse imaging of a representative embryo during compaction shows two cells retracting their memb-mCherry-labelled filopodia just prior to division. H2B-Cerulean-labelled nuclei show chromatin condensation and chromosome separation at the time when filopodia start to retract. Orthogonal scale bar, 5 μm.

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DOI

https://doi.org/10.1038/ncb2875

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