An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos

Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Nature Cell Biology (Impact Factor: 19.68). 12/2009; 12(1):60-5; sup pp 1-9. DOI: 10.1038/ncb2005
Source: PubMed


Partitioning tissues into compartments that do not intermix is essential for the correct morphogenesis of animal embryos and organs. Several hypotheses have been proposed to explain compartmental cell sorting, mainly differential adhesion, but also regulation of the cytoskeleton or of cell proliferation. Nevertheless, the molecular and cellular mechanisms that keep cells apart at boundaries remain unclear. Here we demonstrate, in early Drosophila melanogaster embryos, that actomyosin-based barriers stop cells from invading neighbouring compartments. Our analysis shows that cells can transiently invade neighbouring compartments, especially when they divide, but are then pushed back into their compartment of origin. Actomyosin cytoskeletal components are enriched at compartmental boundaries, forming cable-like structures when the epidermis is mitotically active. When MyoII (non-muscle myosin II) function is inhibited, including locally at the cable by chromophore-assisted laser inactivation (CALI), in live embryos, dividing cells are no longer pushed back, leading to compartmental cell mixing. We propose that local regulation of actomyosin contractibility, rather than differential adhesion, is the primary mechanism sorting cells at compartmental boundaries.

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    • "Simulations of tissue growth with two compartments furthermore suggest that such local increases in cell bond tension can prevent cell mixing between two adjacent cell populations and can account for the straight shape of compartment boundaries (Landsberg et al., 2009; Aliee et al., 2012). Consistent with these data, reducing Myosin II activity, either throughout the tissue or locally along the compartment boundary, compromises boundary shape (Major and Irvine, 2006; Landsberg et al., 2009; Monier et al., 2010; Aliee et al., 2012; Calzolari et al., 2014). Recent data suggest that local increases in cell bond tension bias cell rearrangements to maintain the straight shape of compartment boundaries (Umetsu et al., 2014). "
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    ABSTRACT: Tissue organization requires the interplay between biochemical signaling and cellular force generation. The formation of straight boundaries separating cells with different fates into compartments is important for growth and patterning during tissue development. In the developing Drosophila wing disc, maintenance of the straight anteroposterior (AP) compartment boundary involves a local increase in mechanical tension at cell bonds along the boundary. The biochemical signals that regulate mechanical tension along the AP boundary, however, remain unknown. Here, we show that a local difference in Hedgehog signal transduction activity between anterior and posterior cells is necessary and sufficient to increase mechanical tension along the AP boundary. This difference in Hedgehog signal transduction is also required to bias cell rearrangements during cell intercalations to keep the characteristic straight shape of the AP boundary. Moreover, severing cell bonds along the AP boundary does not reduce tension at neighboring bonds, implying that active mechanical tension is upregulated, cell bond by cell bond. Finally, differences in the expression of the homeodomain-containing protein Engrailed also contribute to the straight shape of the AP boundary, independently of Hedgehog signal transduction and without modulating cell bond tension. Our data reveal a novel link between local differences in Hedgehog signal transduction and a local increase in active mechanical tension of cell bonds that biases junctional rearrangements. The large-scale shape of the AP boundary thus emerges from biochemical signals inducing patterns of active tension on cell bonds.
    Development 11/2015; 142(22):3845-3858. DOI:10.1242/dev.125542 · 6.46 Impact Factor
    • "Much as the tendency to minimize the total free energy associated with surface tension drives the dispersed droplets of immiscible fluids to merge into distinct but homogeneous fluid phases, so too the DAH in its original form proposes that the tendency to minimize total free energy associated with intercellular adhesion drives cell sorting into homogeneous tissue compartments [4]. Using this analogy, the DAH and its extensions attribute macroscopic tissue surface tension to the strength of intercellular adhesion, cell cortical tension and stiffness, and intercellular contraction [2] [5] [6] [9]. But even with these elaborations of the original DAH, the key underlying assumptions are that the tissue behaves dynamically as a fluid, and that the final sorted state corresponds to an equilibrium thermodynamic state, implying minimum free energy. "
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    ABSTRACT: The sorting of distinctly different cell types into specific tissue compartments has long been thought to be a problem in minimization of total free energy in immiscible fluids, wherein cell–cell adhesion, cell stiffness, and cell contraction combine to define an effective macroscopic tissue surface tension. Pawlizak et al (2015 New J. Phys. 17 083049) now show not only that adhesion forces at interfaces unexpectedly fail to correlate with the density of adhesion molecules, but also that certain cancer cell lines unexpectedly fail to behave as a fluid, with cells becoming kinetically trapped in what might be a jammed, solid-like non-equilibrium state.
    New Journal of Physics 09/2015; 17(9). DOI:10.1088/1367-2630/17/9/091001 · 3.56 Impact Factor
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    • "The enrichment of actomyosin cables at boundaries between domains is a feature widely found during development in a variety of tissues. Not only is it present at the interface between rhombomeres and somites, but also at compartmental boundaries in Drosophila embryos and imaginal discs (Aliee et al., 2012; Dahmann et al., 2011; Landsberg et al., 2009; Monier et al., 2010). In all these tissues, the mechanical tension exerted by activated actomyosin maintains cell compartmentalisation. "
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    ABSTRACT: During forebrain morphogenesis, there is extensive reorganisation of the cells destined to form the eyes, telencephalon and diencephalon. Little is known about the molecular mechanisms that regulate region-specific behaviours and that maintain the coherence of cell populations undergoing specific morphogenetic processes. In this study, we show that the activity of the Eph/Ephrin signalling pathway maintains segregation between the prospective eyes and adjacent regions of the anterior neural plate during the early stages of forebrain morphogenesis in zebrafish. Several Ephrins and Ephs are expressed in complementary domains in the prospective forebrain and combinatorial abrogation of their activity results in incomplete segregation of the eyes and telencephalon and in defective evagination of the optic vesicles. Conversely, expression of exogenous Ephs or Ephrins in regions of the prospective forebrain where they are not usually expressed changes the adhesion properties of the cells, resulting in segregation to the wrong domain without changing their regional fate. The failure of eye morphogenesis in rx3 mutants is accompanied by a loss of complementary expression of Ephs and Ephrins, suggesting that this pathway is activated downstream of the regional fate specification machinery to establish boundaries between domains undergoing different programmes of morphogenesis.
    Development 09/2013; 140(20). DOI:10.1242/dev.097048 · 6.46 Impact Factor
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