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Pulsed contractions of an actin–myosin network drive apical constriction


Apical constriction facilitates epithelial sheet bending and invagination during morphogenesis1,2. Apical constriction is conventionally thought to be driven by the continuous purse-string-like contraction of a circumferential actin and non-muscle myosin-II (myosin) belt underlying adherens junctions3,4,5,6,7. However, it is unclear whether other force-generating mechanisms can drive this process. Here we show, with the use of real-time imaging and quantitative image analysis of Drosophila gastrulation, that the apical constriction of ventral furrow cells is pulsed. Repeated constrictions, which are asynchronous between neighbouring cells, are interrupted by pauses in which the constricted state of the cell apex is maintained. In contrast to the purse-string model, constriction pulses are powered by actin–myosin network contractions that occur at the medial apical cortex and pull discrete adherens junction sites inwards. The transcription factors Twist and Snail differentially regulate pulsed constriction. Expression of snail initiates actin–myosin network contractions, whereas expression of twist stabilizes the constricted state of the cell apex. Our results suggest a new model for apical constriction in which a cortical actin–myosin cytoskeleton functions as a developmentally controlled subcellular ratchet to reduce apical area incrementally.

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Figure 1: Apical constriction of ventral furrow cells is pulsed.
Figure 2: Constriction pulses are correlated with myosin coalescence.
Figure 3: Pulsed myosin coalescence and adherens junction bending require an actin–myosin network.
Figure 4: Snail and Twist function at distinct phases of pulsed constriction.


  1. Lecuit, T. & Lenne, P. F. Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nature Rev. Mol. Cell Biol. 8, 633–644 (2007)

    ADS  CAS  Article  Google Scholar 

  2. Leptin, M. Gastrulation movements: the logic and the nuts and bolts. Dev. Cell 8, 305–320 (2005)

    CAS  Article  Google Scholar 

  3. Alberts, B. et al. Molecular Biology of the Cell 5th edn (Garland Science, 2008)

  4. Baker, P. C. & Schroeder, T. E. Cytoplasmic filaments and morphogenetic movement in the amphibian neural tube. Dev. Biol. 15, 432–450 (1967)

    CAS  Article  Google Scholar 

  5. Burnside, B. Microtubules and microfilaments in newt neuralation. Dev. Biol. 26, 416–441 (1971)

    CAS  Article  Google Scholar 

  6. Hildebrand, J. D. Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network. J. Cell Sci. 118, 5191–5203 (2005)

    CAS  Article  Google Scholar 

  7. Karfunkel, P. The activity of microtubules and microfilaments in neurulation in the chick. J. Exp. Zool. 181, 289–301 (1972)

    CAS  Article  Google Scholar 

  8. Dawes-Hoang, R. E. et al. folded gastrulation, cell shape change and the control of myosin localization. Development 132, 4165–4178 (2005)

    CAS  Article  Google Scholar 

  9. Fox, D. T. & Peifer, M. Abelson kinase (Abl) and RhoGEF2 regulate actin organization during cell constriction in Drosophila . Development 134, 567–578 (2007)

    CAS  Article  Google Scholar 

  10. Nikolaidou, K. K. & Barrett, K. A. Rho GTPase signaling pathway is used reiteratively in epithelial folding and potentially selects the outcome of Rho activation. Curr. Biol. 14, 1822–1826 (2004)

    CAS  Article  Google Scholar 

  11. Young, P. E., Pesacreta, T. C. & Kiehart, D. P. Dynamic changes in the distribution of cytoplasmic myosin during Drosophila embryogenesis. Development 111, 1–14 (1991)

    CAS  PubMed  Google Scholar 

  12. Morin, X., Daneman, R., Zavortink, M. & Chia, W. A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila . Proc. Natl Acad. Sci. USA 98, 15050–15055 (2001)

    ADS  CAS  Article  Google Scholar 

  13. Oda, H. & Tsukita, S. Real-time imaging of cell–cell adherens junctions reveals that Drosophila mesoderm invagination begins with two phases of apical constriction of cells. J. Cell Sci. 114, 493–501 (2001)

    CAS  PubMed  Google Scholar 

  14. Sweeton, D., Parks, S., Costa, M. & Wieschaus, E. Gastrulation in Drosophila: the formation of the ventral furrow and posterior midgut invaginations. Development 112, 775–789 (1991)

    CAS  PubMed  Google Scholar 

  15. Vavylonis, D., Wu, J. Q., Hao, S., O’Shaughnessy, B. & Pollard, T. D. Assembly mechanism of the contractile ring for cytokinesis by fission yeast. Science 319, 97–100 (2008)

    ADS  CAS  Article  Google Scholar 

  16. Verkhovsky, A. B., Svitkina, T. M. & Borisy, G. G. Myosin II filament assemblies in the active lamella of fibroblasts: their morphogenesis and role in the formation of actin filament bundles. J. Cell Biol. 131, 989–1002 (1995)

    CAS  Article  Google Scholar 

  17. Svitkina, T. M., Verkhovsky, A. B., McQuade, K. M. & Borisy, G. G. Analysis of the actin–myosin II system in fish epidermal keratocytes: mechanism of cell body translocation. J. Cell Biol. 139, 397–415 (1997)

    CAS  Article  Google Scholar 

  18. Muller, H. A. & Wieschaus, E. armadillo, bazooka, and stardust are critical for early stages in formation of the zonula adherens and maintenance of the polarized blastoderm epithelium in Drosophila . J. Cell Biol. 134, 149–163 (1996)

    CAS  Article  Google Scholar 

  19. Kolsch, V., Seher, T., Fernandez-Ballester, G. J., Serrano, L. & Leptin, M. Control of Drosophila gastrulation by apical localization of adherens junctions and RhoGEF2. Science 315, 384–386 (2007)

    ADS  Article  Google Scholar 

  20. Ip, Y. T., Maggert, K. & Levine, M. Uncoupling gastrulation and mesoderm differentiation in the Drosophila embryo. EMBO J. 13, 5826–5834 (1994)

    CAS  Article  Google Scholar 

  21. Leptin, M. twist and snail as positive and negative regulators during Drosophila mesoderm development. Genes Dev. 5, 1568–1576 (1991)

    CAS  Article  Google Scholar 

  22. Leptin, M. & Grunewald, B. Cell shape changes during gastrulation in Drosophila . Development 110, 73–84 (1990)

    CAS  PubMed  Google Scholar 

  23. Seher, T. C., Narasimha, M., Vogelsang, E. & Leptin, M. Analysis and reconstitution of the genetic cascade controlling early mesoderm morphogenesis in the Drosophila embryo. Mech. Dev. 124, 167–179 (2007)

    CAS  Article  Google Scholar 

  24. Costa, M., Wilson, E. T. & Wieschaus, E. A putative cell signal encoded by the folded gastrulation gene coordinates cell shape changes during Drosophila gastrulation. Cell 76, 1075–1089 (1994)

    CAS  Article  Google Scholar 

  25. Keller, R., Shook, D. & Skoglund, P. The forces that shape embryos: physical aspects of convergent extension by cell intercalation. Phys. Biol. 5, 15007 (2008)

    ADS  Article  Google Scholar 

  26. Royou, A., Sullivan, W. & Karess, R. Cortical recruitment of nonmuscle myosin II in early syncytial Drosophila embryos: its role in nuclear axial expansion and its regulation by Cdc2 activity. J. Cell Biol. 158, 127–137 (2002)

    CAS  Article  Google Scholar 

  27. Franke, J. D., Montague, R. A. & Kiehart, D. P. Nonmuscle myosin II generates forces that transmit tension and drive contraction in multiple tissues during dorsal closure. Curr. Biol. 15, 2208–2221 (2005)

    CAS  Article  Google Scholar 

  28. Edwards, K. A., Demsky, M., Montague, R. A., Weymouth, N. & Kiehart, D. P. GFP–moesin illuminates actin cytoskeleton dynamics in living tissue and demonstrates cell shape changes during morphogenesis in Drosophila . Dev. Biol. 191, 103–117 (1997)

    CAS  Article  Google Scholar 

  29. Arziman, Z., Horn, T. & Boutros, M. E-RNAi: a web application to design optimized RNAi constructs. Nucleic Acids Res. 33, W582–W588 (2005)

    CAS  Article  Google Scholar 

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We thank D. Kiehart and R. Karess for providing flies; J. Goodhouse for assisting with microscopy; and S. De Renzis, X. Lu, T. Schupbach, A. Sokac, F. Ulrich and Y.-C. Wang for helpful comments on the manuscript. This work is supported by grant PF-06-143-01-DDC from the American Cancer Society to A.C.M., National Institutes of Health/National Institute of General Medical Sciences grant P50 GM071508 to M.K., and by National Institute of Child Health and Human Development grant 5R37HD15587 to E.F.W. E.F.W. is an investigator of the Howard Hughes Medical Institute.

Author Contributions Biological reagents and fly stocks were made by A.C.M. and E.F.W., and experiments were performed by A.C.M. Image analysis methods were developed by M.K. and the live-imaging data were analysed by A.C.M. and M.K. The first draft of the manuscript was written by A.C.M. All authors participated in discussion of the data and in producing the final version of the manuscript.

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Correspondence to Eric F. Wieschaus.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures S1- S4 with Legends (PDF 3390 kb)

Supplementary Video 1

Supplementary Video 1 shows a ventral furrow apical constriction visualized with Spider-GFP. The focal plane was adjusted to stay 2 µm below the apical surface along the ventral midline. Time interval between acquired frames was 6 s and the acquisition length was 8 minutes. Video is 36x faster than real-time. (MOV 7419 kb)

Supplementary Video 2

Supplementary Video 2 shows a pulsed constriction of ventral furrow cells. Cell outlines are labelled with Spider-GFP. Time interval between acquired frames was 6 s and the acquisition length was 5 minutes. Video is 72x faster than real-time. (MOV 354 kb)

Supplementary Video 3

Supplementary Video 3 shows that the pulsed constriction is asynchronous. The colour of the cell indicates the constriction rate (as illustrated by the colour bar in Fig. 1h) for a given time point. Time interval between acquired frames was 6s and the acquisition length was 6 minutes. Video is 18x faster than real-time. (MOV 2533 kb)

Supplementary Video 4

Supplementary Video 4 shows apical myosin dynamics during ventral furrow cell apical constriction. Z-projections of Myosin-mCherry (green, 5 µm depth) are merged with a single Spider-GFP z-slice located 2 µm below the apical cortex (red). Time interval between acquired frames was 5 s and the acquisition length was 7.5 minutes. Video is 25x faster than real-time. (MOV 11170 kb)

Supplementary Video 5

Supplementary Video 5 shows that myosin coalescence accompanies apical constriction. Z-projections of Myosin-mCherry (green, 5 µm depth) are merged with a single Spider-GFP z-slice located 2 µm below the apical cortex (red and bottom). Time interval between acquired frames was 6 s and the acquisition length was 2.6 minutes. Video is 50x faster than real-time. (MOV 770 kb)

Supplementary Video 6

Supplementary Video 6 shows that .Twist and Snail differentially regulate myosin dynamics. Z-projections of Myosin-GFP (5 µm depth) for the indicated genetic backgrounds. Note that myosin coalescence is more prominent in twist mutant embryos than snail mutant embryos. This results in more movement of myosin structures since they are being pulled. Time interval between acquired frames was 10 s and the acquisition length was 16.7 minutes. Video is 100x faster than real-time. (MOV 18122 kb)

Supplementary Video 7

Supplementary Video 7 shows that. twistRNAi and snailRNAi mimic the mutant phenotypes. Z-projections of Myosin-GFP for the indicated knock-downs. Time interval between acquired frames was 10 s and the acquisition length was 16.7 minutes. Video is 100x faster than real-time. Note that the phenotypes are not as severe as the null mutants, probably due to remaining Twist and Snail activity. (MOV 10269 kb)

Supplementary Video 8

Supplementary Video 8 shows that the Constriction pulses in twistRNAi embryos are not stabilized. Cell outlines 2 µm below the apical cortex are labelled using SpiderGFP. Cell shape is relatively constant in snailRNAi embryos, while fluctuations in cell size and shape occur in twistRNAi embryos. Time interval between acquired frames was 6 s and the acquisition length was 7 minutes. Video is 36x faster than real-time. (MOV 10159 kb)

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Martin, A., Kaschube, M. & Wieschaus, E. Pulsed contractions of an actin–myosin network drive apical constriction. Nature 457, 495–499 (2009).

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