[en] Animal development consists of a cascade of tissue differentiation and shape change. Associated mechanical signals regulate tissue differentiation. Here we demonstrate that endogenous mechanical cues also trigger biochemical pathways, generating the active morphogenetic movements shaping animal development through a mechanotransductive cascade of Myo-II medio-apical stabilization. To mimic physiological tissue deformation with a cell scale resolution, liposomes containing magnetic nanoparticles are injected into embryonic epithelia and submitted to time-variable forces generated by a linear array of micrometric soft magnets. Periodic magnetically induced deformations quantitatively phenocopy the soft mechanical endogenous snail-dependent apex pulsations, rescue the medio-apical accumulation of Rok, Myo-II and subsequent mesoderm invagination lacking in sna mutants, in a Fog-dependent mechanotransductive process. Mesoderm invagination then activates Myo-II apical accumulation, in a similar Fog-dependent mechanotransductive process, which in turn initiates endoderm invagination. This reveals the existence of a highly dynamic self-inductive cascade of mesoderm and endoderm invaginations, regulated by mechano-induced medio-apical stabilization of Myo-II.
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).
Zallen, J. A., Wieschaus, E. Patterned gene expression directs bipolar polarity in drosophila. Dev. Cell 6, 343-355 (2004).
Bertet, C., Sulak, L., Lecuit, T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667-671 (2004).
Butler, L. C., et al. Cell shape changes indicate a role for extrinsic tensile forces in Drosophila germ-band extension. Nat. Cell. Biol. 11, 859-864 (2009).
Sagner, A., et al. Establishment of global patterns of planar polarity during growth of the Drosophila wing epithelium. Curr. Biol. 22, 1296-1301 (2012).
Bosveld, F., et al. Mechanical control of morphogenesis by Fat/Dachsous/Fourjointed planar cell polarity pathway. Science 336, 724-727 (2012).
Aliee, M., et al. Physical mechanisms shaping the Drosophila dorsoventral compartment boundary. Curr. Biol. 22, 967-976 (2012).
Rozbicki, E., et al. Myosin-II-mediated cell shape changes and cell intercalation contribute to primitive streak formation. Nat. Cell Biol. 17, 397-408 (2015).
Naganathan, S. R., Furthauer, S., Nishikawa, M., Julicher, F., Grill, S. W. Active torque generation by the actomyosin cell cortex drives left-right symmetry breaking. eLife 3, e04165 (2014).
Wozniak, M., Chen, C. S. Mechano-tranduction: a growing role for contractibility. Nat. Rev. Mol. Cell Biol. 10, 34-43 (2009).
Mammoto, T., Ingber, D. E. Mechanical control of tissue and organ development. Development 137, 1407-1420 (2010).
Farge, E. Mechanotransduction in development. Curr. Top. Dev. Biol. 95, 243-265 (2011).
Desprat, N., Supatto, W., Pouille, P. A., Beaurepaire, E., Farge, E. Tissue deformation modulates twist expression to determine anterior midgut differentiation in Drosophila embryos. Dev. Cell. 15, 470-477 (2008).
Brunet, T., et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nat. Commun. 4, 2821 (2013).
Hiramatsu, R., et al. External mechanical cues trigger the establishment of the anterior-posterior axis in early mouse embryos. Dev. Cell 27, 131-144 (2013).
Mammoto, T., et al. Mechanochemical control of mesenchymal condensation and embryonic tooth organ formation. Dev. Cell 21, 758-769 (2011).
Kahn, J., et al. Muscle contraction is necessary to maintain joint progenitor cell fate. Dev. Cell 16, 734-743 (2009).
Pouille, P. A., Ahmadi, P., Brunet, A. C., Farge, E. Mechanical signals trigger myosin ii redistribution and mesoderm invagination in Drosophila embryos. Sci. Signal. 2, ra16 (2009).
Monier, B., et al. Apico-basal forces exerted by apoptotic cells drive epithelium folding. Nature 12, 245-248 (2015).
Fernandez-Gonzalez, R., Simoes Sde, M., Roper, J. C., Eaton, S., Zallen, J. A. Myosin II dynamics are regulated by tension in intercalating cells. Dev. Cell 17, 736-743 (2009).
Bardet, P. L., et al. PTEN controls junction lengthening and stability during cell rearrangement in epithelial tissue. Dev. Cell 25, 534-546 (2013).
Hamant, O., et al. Developmental patterning by mechanical signals in Arabidopsis. Science 322, 1650-1655 (2008).
Uyttewaal, M., et al. Mechanical stress acts via katanin to amplify differences in growth rate between adjacent cells in Arabidopsis. Cell 149, 439-451 (2012).
Collinet, C., Rauzi, M., Lenne, P. F., Lecuit, T. Local and tissue-scale forces drive oriented junction growth during tissue extension. Nat. Cell Biol. 17, 1247-1258 (2015).
Lye, C. M., et al. Mechanical coupling between endoderm invagination and axis extension in Drosophila. PLoS Biol. 13, e1002292 (2015).
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).
Leptin, M. Twist and snail as positive and negative regulators during Drosophila mesoderm development. Genes Dev. 5, 1568-1576 (1991).
Martin, A. C., Kaschube, M., Wieschaus, E. F. Pulsed contractions of an actinmyosin network drive apical constriction. Nature 457, 495-499 (2009).
Spemann, H., Mangold, H. Foundations of Experimental Embryology 144-184 (Hafner, 1924).
Gilbert, S. F. Developmental Biology 11th edn (Sinauer Associates, 2016).
Martin, A. C. Pulsation and stabilization: contractile forces that underlie morphogenesis. Dev. Biol. 341, 114-125 (2009).
Wang, Y., et al. ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ. Res. 104, 531-540 (2009).
Monier, B., Pelissier-Monier, A., Brand, A. H., Sanson, B. An actomyosinbased barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos. Nat. Cell Biol. 12, 60-65 (2010).
Bealle, G., et al. Ultra magnetic liposomes for MR imaging, targeting, and hyperthermia. Langmuir 28, 11834-11842 (2012).
Feynman, R. P. The Feynman Lectures on Physics (Addison-Wesley Publishing Company, 1964).
Etoc, F., et al. Magnetogenetic control of protein gradients inside living cells with high spatial and temporal resolution. Nano. Lett. 15, 3487-3494 (2015).
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).
Mason, F. M., Tworoger, M., Martin, A. C. Apical domain polarization localizes actin-myosin activity to drive ratchet-like apical constriction. Nat. Cell Biol. 15, 926-936 (2013).
Morize, P., Christiansen, A. E., Costa, M., Parks, S., Wieschaus, E. Hyperactivation of the folded gastrulation pathway induces specific cell shape changes. Development 125, 589-597 (1998).
Alberga, A., Boulay, J. L., Kempe, E., Dennefeld, C., Haenlin, M. The snail gene required for mesoderm formation in Drosophila is expressed dynamically in derivatives of all three germ layers. Development 111, 983-992 (1991).
Costa, M., Sweeton, D., Wieschaus, E. in The Development of Drosophila Melanogaster (eds Bate, M., Martinez-Arias, A.) 425-464 (Cold Spring Harbor Laboratory Press, 1993).
Kustov, M., et al. Magnetic characterization of micropatterned Nd-Fe-B hard magnetic films using scanning Hall probe microscopy. J. Appl. Phys. 108, 063914 (2010).
Wieschaus, E., Sweeton, D., Costa, M. in Gastrulation (ed. Keller, R.) 213-223 (Plenum Press, 1991).
Farge, E. Mechanical induction of twist in the Drosophila foregut/stomodeal primordium. Curr. Biol. 13, 1365-1377 (2003).
Arendt, D. in Gastrulation-From Cells to Embryo (ed. Stern, C. D., Cold Spring Harbor Laboratory press, 2004).
Dawes-Hoang, R. E., et al. folded gastrulation, cell shape change and the control of myosin localization. Development 132, 4165-4178 (2005).
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).
Driquez, B., Bouclet, A., Farge, E. Mechanotransduction in mechanically coupled pulsating cells: transition to collective constriction and mesoderm invagination simulation. Phys. Biol. 8, 066007 (2011).
Xie, S., Martin, A. C. Intracellular signalling and intercellular coupling coordinate heterogeneous contractile events to facilitate tissue folding. Nat. Commun. 6, 7161 (2015).
Manning, A. J., Peters, K. A., Peifer, M., Rogers, S. L. Regulation of epithelial morphogenesis by the G protein-coupled receptor mist and its ligand fog. Sci. Signal. 6, ra98 (2013).
Fernandez-Sanchez, M. E., Brunet, T., Roper, J. C., Farge, E. Mechanotransduction's impact in animal development, evolution, and tumorigenesis. Annu. Rev. Cell Dev. Biol. 31, 373-397 (2015).
Odell, G. M., Oster, G., Alberch, P., Burnside, B. The mechanical basis of morphogenesis. I. Epithelial folding and invagination. Dev. Biol. 85, 446-462 (1981).
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).
Weng, M., Wieschaus, E. Myosin-dependent remodeling of adherens junctions protects junctions from Snail-dependent disassembly. J. Cell Biol. 212, 219-229 (2016).
Roth, S. Mechanisms of dorsal-ventral axis determination in Drosophila embryos revealed by cytoplasmic transplantations. Development 117, 1385-1396 (1993).
Xia, L., et al. The niche-dependent feedback loop generates a BMP activity gradient to determine the germline stem cell fate. Curr. Biol. 22, 515-521 (2012).
Xu, Z., et al. Impacts of the ubiquitous factor Zelda on Bicoiddependent DNA binding and transcription in Drosophila. Genes Dev. 28, 608-621 (2014).
Luk, S. K., Kilpatrick, M., Kerr, K., Macdonald, P. M. Components acting in localization of bicoid mRNA are conserved among Drosophila species. Genetics 137, 521-530 (1994).
Gavis, E. R., Lehmann, R. Localization of nanos RNA controls embryonic polarity. Cell 71, 301-313 (1992).
Thisse, C., Perrin-Schmitt, F., Stoetzel, C., Thisse, B. Sequence-specific transactivation of the Drosophila twist gene by the dorsal gene product. Cell 65, 1191-1201 (1991).
Massart, R. Preparation of aqueous magnetic liquids in alkaline and acidic media. IEEE Trans. Magn. 17, 1247-1248 (1981).
Skoza, F. C., Papahadjopoulos, D. Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc. Natl Acad. Sci. USA 75, 4194-4198 (1978).
Le Roy, D., et al. Fabrication and characterization of polymer membranes with integrated arrays of high performance micro-magnets. Mater. Today Commun. 6, 50 (2016).
Shaw, G., Kramer, R. B. G., Dempsey, N. M., Hasselbach, K., et al. A scanning Hall probe microscope for high resolution, large area, variable height magnetic field imaging. Review of Scientific Instruments 87, 113702 (2016).
Desprat, N., Supatto, W., Pouille, P.-A., Beaurepaire, E., Farge, E. Tissue deformation modulates twist expression to determine anterior midgut differentiation in Drosophila embryos. Dev. Cell 15, 470-477 (2008).
