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Planar polarized actomyosin contractile flows control epithelial junction remodelling

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Abstract

Force generation by Myosin-II motors on actin filaments drives cell and tissue morphogenesis1,2,3,4,5,6,7,8,9,10,11,12,13,14,15. In epithelia, contractile forces are resisted at apical junctions by adhesive forces dependent on E-cadherin16, which also transmits tension6,17,18,19. During Drosophila embryonic germband extension, tissue elongation is driven by cell intercalation20, which requires an irreversible and planar polarized remodelling of epithelial cell junctions4,5. We investigate how cell deformations emerge from the interplay between force generation and cortical force transmission during this remodelling in Drosophila melanogaster. The shrinkage of dorsal–ventral-oriented (‘vertical’) junctions during this process is known to require planar polarized junctional contractility by Myosin II (refs 4, 5, 7, 12). Here we show that this shrinkage is not produced by junctional Myosin II itself, but by the polarized flow of medial actomyosin pulses towards ‘vertical’ junctions. This anisotropic flow is oriented by the planar polarized distribution of E-cadherin complexes, in that medial Myosin II flows towards ‘vertical’ junctions, which have relatively less E-cadherin than transverse junctions. Our evidence suggests that the medial flow pattern reflects equilibrium properties of force transmission and coupling to E-cadherin by α-Catenin. Thus, epithelial morphogenesis is not properly reflected by Myosin II steady state distribution but by polarized contractile actomyosin flows that emerge from interactions between E-cadherin and actomyosin networks.

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Figure 1: Two pulsating pools of acto-myosin in intercalating cells.
Figure 2: Medial and junctional Myo-II pools have different mechanical roles.
Figure 3: Medial Myosin-II displays anisotropic flow and feeds ‘vertical’ junctions.
Figure 4: E-cadherin planar polarity orients medial Myosin-II flow.

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Change history

  • 17 February 2011

    The present address for author M.Z. was corrected on 17 February 2011

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Acknowledgements

We thank R. Levayer, M. Mavrakis and J.-M. Philippe for making and sharing respectively the utrophin–GFP, GAP43–Venus and GAP43–Cherry transgenic lines. We are grateful to our colleagues for their gifts of reagents: B. Bement, R. Karess, H. Oda, A. Martin and E. Wieschaus. We thank E. Munro and all members of the Lecuit and Lenne groups for discussions, and comments on the manuscript. This work was supported by a Programme Grant from HFSP to T.L, P.-F.L and E. Munro, by the CNRS, the Fondation pour la Recherche Médicale (to T.L), the ANR-Blanc 2005 (to T.L. and P.-F.L), Région PACA and ANR-PCV 2008 (to P.-F.L and T.L.). M.R. was supported by a PhD fellowship by the Région PACA and Amplitude Systems.

Author information

Authors and Affiliations

Authors

Contributions

M.R. made the original observations of pulsed contractility and flow. M.R. and T.L. planned the project, and analysed the data together with P.-F.L.; M.R. conducted the experiments except for FRAP experiments on MRLC–GFP, which were performed by P.-F.L. and T.L.; P.-F.L. and M.R. developed the nano-ablation system. T.L. and P.-F.L. wrote the manuscript together with M.R. All authors commented on the manuscript.

Corresponding authors

Correspondence to Pierre-François Lenne or Thomas Lecuit.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

The file contains Supplementary Figures 1-12 with legends. (PDF 4965 kb)

Supplementary Movie 1a

Time lapse movie of Utrophin::GFP (labelling F-actin) in intercalating cells of a wild type embryo, 15-20 min after the onset of gastrulation. The focal plane is at the apical most position near the plasma membrane. Scale bar: 5 μm. (MOV 11774 kb)

Supplementary Movie 1b

Time lapse movie of Utrophin::GFP (labelling F-actin) in intercalating cells of a wild type embryo, 15-20 min after the onset of gastrulation. The focal plane is at a slightly less apical focal plane, intersecting the adherens junctions. Scale bar: 5 μm. (MOV 2076 kb)

Supplementary Movie 2

Time lapse movie of MRLC::GFP (Myo-II) in intercalating cells of a wild type embryo, 15-20 min after the onset of gastrulation. Each image is the projection of a 3 μm zstack. Scale bar: 5 μm. (MOV 5680 kb)

Supplementary Movie 3

Time lapse movie of MRLC::Cherry (red) and Utr ::GFP (green) in the apical region of intercalating cells of a wild type embryo (MOV 5547 kb)

Supplementary Movie 4

Time lapse movie of MRLC::GFP (Myo-II) in intercalating cells of a wild type embryo. Nano dissection (< 400 nm, red arrowhead) of medial Myo-II, 15-20 min after the onset of gastrulation. Scale bar: 5μm. (MOV 1599 kb)

Supplementary Movie 5

Time lapse movie of MRLC::GFP (Myo-II) in intercalating cells of a wild type embryo,, 20 min after the onset of gastrulation. Each image is the projection of a 3 μm zstack.. Coloured traces represent the trajectory of coalescing speckles of medial Myo- II. Scale bar: 5 μm. (MOV 16638 kb)

Supplementary Movie 6

Time lapse movie of MRLC::GFP (Myo-II) in cells of a krüppel RNAi injected embryo,15-20 min after the onset of gastrulation. Each image is the projection of a 3 μm z-stack. Scale bar: 5 μm. (MOV 1790 kb)

Supplementary Movie 7

Time lapse movie of MRLC::GFP (Myo-II) in cells of a wild type embryo. Each image is the projection of a 3 μm z-stack. The most apical planes of the 3 μm stack (500 nm projection) are shown in green while the most basal (2.5 μm projection) are shown in red. Scale bar: 5 μm. (MOV 694 kb)

Supplementary Movie 8

Time lapse movie and FRAP of MRLC::GFP (Myo-II) in cells of a wild type embryo. Each image is the projection of a 3 μm z-stack. FRAP is performed on the junctional pool of Myo-II at time 0 seconds. Clusters of Myo-II from the medial pool are then transferred to the cortex. Scale bar: 5 μm. (MOV 3966 kb)

Supplementary Movie 9

Time lapse movie of GAP43::Venus (plasma membrane) in the apical region of intercalating cells. Note the relative flat organization of the apical surface. Scale bar: 5 μm. (MOV 12592 kb)

Supplementary Movie 10

Time lapse movie of GAP43::Venus (plasma membrane) in the apical region of apically constricting mesoderm cells. Note the strongly ruffled apical surface. Scale bar: 5μm. (MOV 1540 kb)

Supplementary Movie 11

Time lapse movie of GAP43::Cherry (plasma membrane, red, middle) and Utr::GFP (F-actin, green, right) in the apical region of intercalating cells. The trajectories of a small protrusion (red dot in middle panel) and of an actin patch (green dot in right panel) are shown. Scale bar: 5 μm. (MOV 591 kb)

Supplementary Movie 12

Time lapse movie of GAP43::Cherry (plasma membrane, red, middle) and Utr::GFP (F-actin, green, right) in the apical region of intercalating cells. The trajectories of a small protrusion (red dot in middle panel) and of an actin patch (green dot in right panel) are shown. Scale bar: 5 μm. (MOV 1072 kb)

Supplementary Movie 13

Time lapse movie of MRLC::Cherry (Myo-II) and E-cad::GFP in intercalating cells of a wild type embryo, 15-20 min after the onset of gastrulation. Each image is the projection of a 3 μm z-stack. Left panel: merged signal of MRLC::Cherry (green) and E-cad::GFP (red); central panel: E-cad::GFP; right panel: MRLC::Cherry. Scale bar: 5 μm. (MOV 8127 kb)

Supplementary Movie 14

Time lapse movie of MRLC::Cherry (displayed in green) and E-cad::GFP (displayed in red) in an E-cad RNAi embryo, 15-20 min after the presumptive onset of gastrulation. Each image is the projection of a 3 μm z-stack. Scale bar: 5 μm. (MOV 6012 kb)

Supplementary Movie 15

Time lapse movie of MRLC::Cherry (displayed in green) and E-cad::GFP (displayed in red) in an α-cat RNAi embryo, 15-20 min after the presumptive onset of gastrulation. Each image is the projection of a 3 μm z-stack. Scale bar: 5 μm. (MOV 9159 kb)

Supplementary Movie 16

Time lapse movie of MRLC::Cherry (displayed in green) and E-cad::GFP (displayed in red) in intercalating cells of a wild type embryo, 15-20 min after the onset of gastrulation. Nanodissectionof medial Myo-II is indicated by a white arrowhead. The left panel shows the trajectory of the remaining cluster of medial Myo-II after ablation. Scale bar: 5 μm. (MOV 509 kb)

Supplementary Movie 17

Time lapse movie of Utr::GFP (F-actin) in intercalating cells of a wild type embryo. Nanodissection of the medial F-actin meshwork is indicated by a red arrowhead. Note the relaxation of the meshwork following ablation. Scale bar: 5 μm. (MOV 1114 kb)

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Rauzi, M., Lenne, PF. & Lecuit, T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature 468, 1110–1114 (2010). https://doi.org/10.1038/nature09566

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