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  • Review Article
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Programmed and self-organized flow of information during morphogenesis

Nature Reviews Molecular Cell Biology volume 22, pages 245–265 (2021)Cite this article

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Abstract

How the shape of embryos and organs emerges during development is a fundamental question that has fascinated scientists for centuries. Tissue dynamics arise from a small set of cell behaviours, including shape changes, cell contact remodelling, cell migration, cell division and cell extrusion. These behaviours require control over cell mechanics, namely active stresses associated with protrusive, contractile and adhesive forces, and hydrostatic pressure, as well as material properties of cells that dictate how cells respond to active stresses. In this Review, we address how cell mechanics and the associated cell behaviours are robustly organized in space and time during tissue morphogenesis. We first outline how not only gene expression and the resulting biochemical cues, but also mechanics and geometry act as sources of morphogenetic information to ultimately define the time and length scales of the cell behaviours driving morphogenesis. Next, we present two idealized modes of how this information flows — how it is read out and translated into a biological effect — during morphogenesis. The first, akin to a programme, follows deterministic rules and is hierarchical. The second follows the principles of self-organization, which rests on statistical rules characterizing the system’s composition and configuration, local interactions and feedback. We discuss the contribution of these two modes to the mechanisms of four very general classes of tissue deformation, namely tissue folding and invagination, tissue flow and extension, tissue hollowing and, finally, tissue branching. Overall, we suggest a conceptual framework for understanding morphogenetic information that encapsulates genetics and biochemistry as well as mechanics and geometry as information modules, and the interplay of deterministic and self-organized mechanisms of their deployment, thereby diverging considerably from the traditional notion that shape is fully encoded and determined by genes.

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Fig. 1: Programme versus self-organization in the flow of morphogenetic information.
Fig. 2: Polarized contractility drives tissue bending and invagination.
Fig. 3: Growth-driven mechanical instabilities drive tissue folding and looping.
Fig. 4: Tissue extension by programmed polarization of cellular active stresses.
Fig. 5: Impact of patterned boundaries and their geometry in tissue flows and extension.
Fig. 6: Mechanical and geometrical feedbacks control lumen formation to regulate tissue size and patterning.
Fig. 7: Morphogenesis of branched structures can be genetically programmed or emerge as self-organized.

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References

  1. Waddington, C. H. The Strategy of the Genes: a Discussion of Some Aspects of Theoretical Biology (George Allen and Unwin, London, 1957).

  2. Slack, J. M. Conrad Hal Waddington: the last renaissance biologist? Nat. Rev. Genet. 3, 889–895 (2002).

    CAS  PubMed  Google Scholar 

  3. Roux, W. in Foundations of Experimental Embryology (eds Willier, B. H. & Oppenheimer, J. M.) 2–37 (Hafner, 1888).

  4. De Robertis, E. M. Spemann’s organizer and self-regulation in amphibian embryos. Nat. Rev. Mol. Cell Biol. 7, 296–302 (2006).

    PubMed  PubMed Central  Google Scholar 

  5. Sulston, J. E., Schierenberg, E., White, J. G. & Thomson, J. N. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100, 64–119 (1983).

    CAS  PubMed  Google Scholar 

  6. Maduro, M. F. Cell fate specification in the C. elegans embryo. Dev. Dyn. 239, 1315–1329 (2010).

    CAS  PubMed  Google Scholar 

  7. Nishida, H. & Stach, T. Cell lineages and fate maps in tunicates: conservation and modification. Zool. Sci. 31, 645–652 (2014).

    Google Scholar 

  8. Garcia-Bellido, A. & Santamaria, P. Developmental analysis of the wing disc in the mutant engrailed of Drosophila melanogaster. Genetics 72, 87–104 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Pradel, J. & White, R. A. From selectors to realizators. Int. J. Dev. Biol. 42, 417–421 (1998).

    CAS  PubMed  Google Scholar 

  10. Halder, G., Callaerts, P. & Gehring, W. J. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267, 1788–1792 (1995).

    CAS  PubMed  Google Scholar 

  11. Halder, G., Callaerts, P. & Gehring, W. J. New perspectives on eye evolution. Curr. Opin. Genet. Dev. 5, 602–609 (1995).

    CAS  PubMed  Google Scholar 

  12. Chanut-Delalande, H., Fernandes, I., Roch, F., Payre, F. & Plaza, S. Shavenbaby couples patterning to epidermal cell shape control. PLoS Biol. 4, e290 (2006).

    PubMed  PubMed Central  Google Scholar 

  13. Driesch, H. The potency of the first two cleavage cells in echinoderm development: experimental production of double and partial formation. Reprinted in Foundations of Experimental Embryology (eds Willier, B. H. & Oppenheimer, J. M.) (Hafner, 1892).

  14. Morgan, T. H. Half-embryos and whole-embryos from one of the first two blastomeres of the frog’s egg. Anat. Anz. 10, 623–628 (1895).

    Google Scholar 

  15. Spemann, H. Embryonic Development and Induction, Vol. 10 (Taylor & Francis, 1988).

  16. Browne, E. N. The production of new hydranths in Hydra by the insertion of small grafts. J. Exp. Zool. 7, 1–23 (1909).

    Google Scholar 

  17. Spemann, H. & Mangold, H. Induction of embryonic primordia by implantation of organizers from a different species. Roux Arch. Entwickl. Mech. 100, 599–638 (1924).

    Google Scholar 

  18. Gilmour, D., Rembold, M. & Leptin, M. From morphogen to morphogenesis and back. Nature 541, 311–320 (2017).

    CAS  PubMed  Google Scholar 

  19. Hannezo, E. & Heisenberg, C. P. Mechanochemical feedback loops in development and disease. Cell 178, 12–25 (2019).

    CAS  PubMed  Google Scholar 

  20. Schweisguth, F. & Corson, F. Self-organization in pattern formation. Dev. Cell 49, 659–677 (2019).

    CAS  PubMed  Google Scholar 

  21. Turing, A. M. The chemical basis of morphogenesis. Philos. Trans. R. Soc. London. Ser. B, Biol. Sci. 237, 37–72 (1952).

    Google Scholar 

  22. Prusinkiewicz, P., Meinhardt, H. & Fowler, D. R. The Algorithmic Beauty of Sea Shells (Springer, 2003).

  23. Gelens, L., Anderson, G. A. & Ferrell, J. E. Jr. Spatial trigger waves: positive feedback gets you a long way. Mol. Biol. Cell 25, 3486–3493 (2014).

    PubMed  PubMed Central  Google Scholar 

  24. Wartlick, O. et al. Dynamics of Dpp signaling and proliferation control. Science 331, 1154–1159 (2011).

    CAS  PubMed  Google Scholar 

  25. Rogers, K. W. & Schier, A. F. Morphogen gradients: from generation to interpretation. Annu. Rev. Cell Dev. Biol. 27, 377–407 (2011).

    CAS  PubMed  Google Scholar 

  26. Sagner, A. & Briscoe, J. Morphogen interpretation: concentration, time, competence, and signaling dynamics. Wiley Interdiscip. Rev. Dev. Biol. 6, e271 (2017).

    PubMed Central  Google Scholar 

  27. Economou, A. D. et al. Periodic stripe formation by a Turing mechanism operating at growth zones in the mammalian palate. Nat. Genet. 44, 348–351 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Sheth, R. et al. Hox genes regulate digit patterning by controlling the wavelength of a Turing-type mechanism. Science 338, 1476–1480 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Pourquie, O. The segmentation clock: converting embryonic time into spatial pattern. Science 301, 328–330 (2003).

    CAS  PubMed  Google Scholar 

  30. Mayer, M., Depken, M., Bois, J. S., Julicher, F. & Grill, S. W. Anisotropies in cortical tension reveal the physical basis of polarizing cortical flows. Nature 467, 617–621 (2010).

    CAS  PubMed  Google Scholar 

  31. Clement, R., Dehapiot, B., Collinet, C., Lecuit, T. & Lenne, P. F. Viscoelastic dissipation stabilizes cell shape changes during tissue morphogenesis. Curr. Biol. 27, 3132–3142 e3134 (2017).

    CAS  PubMed  Google Scholar 

  32. Dasbiswas, K., Hannezo, E. & Gov, N. S. Theory of epithelial cell shape transitions induced by mechanoactive chemical gradients. Biophys. J. 114, 968–977 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Dicko, M. et al. Geometry can provide long-range mechanical guidance for embryogenesis. PLoS Comput. Biol. 13, e1005443 (2017).

    PubMed  PubMed Central  Google Scholar 

  34. Oster, G. F., Murray, J. D. & Harris, A. K. Mechanical aspects of mesenchymal morphogenesis. J. Embryol. Exp. Morphol. 78, 83–125 (1983).

    CAS  PubMed  Google Scholar 

  35. Shyer, A. E. et al. Emergent cellular self-organization and mechanosensation initiate follicle pattern in the avian skin. Science 357, 811–815 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Hannezo, E., Dong, B., Recho, P., Joanny, J. F. & Hayashi, S. Cortical instability drives periodic supracellular actin pattern formation in epithelial tubes. Proc. Natl Acad. Sci. USA 112, 8620–8625 (2015).

    CAS  PubMed  Google Scholar 

  37. Ladoux, B., Nelson, W. J., Yan, J. & Mège, R. M. The mechanotransduction machinery at work at adherens junctions. Integr. Biol. 7, 1109–1119 (2015).

    CAS  Google Scholar 

  38. Collinet, C. & Lecuit, T. Stability and dynamics of cell-cell junctions. Prog. Mol. Biol. Transl Sci. 116, 25–47 (2013).

    CAS  PubMed  Google Scholar 

  39. Papusheva, E. & Heisenberg, C.-P. Spatial organization of adhesion: force-dependent regulation and function in tissue morphogenesis. EMBO J. 29, 2753–2768 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Schwayer, C. et al. Mechanosensation of tight junctions depends on ZO-1 phase separation and flow. Cell 179, 937–952 e918 (2019).

    CAS  PubMed  Google Scholar 

  41. Lecuit, T., Lenne, P. F. & Munro, E. Force generation, transmission, and integration during cell and tissue morphogenesis. Annu. Rev. Cell Dev. Biol. 27, 157–184 (2011).

    CAS  PubMed  Google Scholar 

  42. Geiger, B., Spatz, J. P. & Bershadsky, A. D. Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell Biol. 10, 21–33 (2009).

    CAS  PubMed  Google Scholar 

  43. Bailles, A. et al. Genetic induction and mechanochemical propagation of a morphogenetic wave. Nature 572, 467–473 (2019). Shows that a mechano-chemical wave of Rho1–MyoII activation drives invagination and anterior movement of the posterior endoderm during D. melanogaster gastrulation. It shows the relevance of self-organized contractile waves in driving tissue invagination and movements.

    CAS  PubMed  Google Scholar 

  44. Kindberg, A., Hu, J. K. & Bush, J. O. Forced to communicate: integration of mechanical and biochemical signaling in morphogenesis. Curr. Opin. Cell Biol. 66, 59–68 (2020).

    CAS  PubMed  Google Scholar 

  45. Munjal, A., Philippe, J. M., Munro, E. & Lecuit, T. A self-organized biomechanical network drives shape changes during tissue morphogenesis. Nature 524, 351–355 (2015). Shows how pulsed contractility during D. melanogaster germband extension depends on self-organizational properties of actomyosin networks, that is, an advection-mediated positive feedback on MyoII activation due to the association of Rho1GTP, Rok to actomyosin cortex.

    CAS  PubMed  Google Scholar 

  46. Goehring, N. W. et al. Polarization of PAR proteins by advective triggering of a pattern-forming system. Science 334, 1137–1141 (2011).

    CAS  PubMed  Google Scholar 

  47. Michaux, J. B., Robin, F. B., McFadden, W. M. & Munro, E. M. Excitable RhoA dynamics drive pulsed contractions in the early C. elegans embryo. J. Cell Biol. 217, 4230–4252 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Durdu, S. et al. Luminal signalling links cell communication to tissue architecture during organogenesis. Nature 515, 120–124 (2014).

    CAS  PubMed  Google Scholar 

  49. Shyer, A. E., Huycke, T. R., Lee, C., Mahadevan, L. & Tabin, C. J. Bending gradients: how the intestinal stem cell gets its home. Cell 161, 569–580 (2015). Shows that mechanical buckling of intestinal villi in chick and mouse embryos distorts a chemical gradient of SHH and restricts stem cell proliferation at the villus base. It shows the relevance of tissue geometry in shaping the morphogenetic information.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Martin, A. C. & Goldstein, B. Apical constriction: themes and variations on a cellular mechanism driving morphogenesis. Development 141, 1987–1998 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Munjal, A. & Lecuit, T. Actomyosin networks and tissue morphogenesis. Development 141, 1789–1793 (2014).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  53. 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 

  54. Martin, A. C., Kaschube, M. & Wieschaus, E. F. Pulsed contractions of an actin–myosin network drive apical constriction. Nature 457, 495–499 (2009). Shows that cell apical constriction during invagination of the mesoderm in D. melanogaster is driven by medio-apical actomyosin pulsed contractions instead of purse-string contractility at adherens junctions as previously thought.

    CAS  PubMed  Google Scholar 

  55. Gelbart, M. A. et al. Volume conservation principle involved in cell lengthening and nucleus movement during tissue morphogenesis. Proc. Natl Acad. Sci. USA 109, 19298–19303 (2012).

    CAS  PubMed  Google Scholar 

  56. Krueger, D., Tardivo, P., Nguyen, C. & De Renzis, S. Downregulation of basal myosin-II is required for cell shape changes and tissue invagination. EMBO J. 37, e100170, https://doi.org/10.15252/embj.2018100170 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gracia, M. et al. Mechanical impact of epithelial-mesenchymal transition on epithelial morphogenesis in Drosophila. Nat. Commun. 10, 2951 (2019).

    PubMed  PubMed Central  Google Scholar 

  58. Sherrard, K., Robin, F., Lemaire, P. & Munro, E. Sequential activation of apical and basolateral contractility drives ascidian endoderm invagination. Curr. Biol. 20, 1499–1510 (2010). Identifies a two-step mechanism for endoderm invagination in ascidian embryos: first, a Rho1–ROCK–MyoII-mediated phase of cell apical constriction and second, a phase of apico-basal shortening dependent on MyoII but not on Rho1–ROCK. It shows the relevance of polarized actomyosin contractility in driving 3D cell shape changes during invagination.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Vasquez, C. G., Tworoger, M. & Martin, A. C. Dynamic myosin phosphorylation regulates contractile pulses and tissue integrity during epithelial morphogenesis. J. Cell Biol. 206, 435–450 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Izquierdo, E., Quinkler, T. & De Renzis, S. Guided morphogenesis through optogenetic activation of Rho signalling during early Drosophila embryogenesis. Nat. Commun. 9, 2366 (2018).

    PubMed  PubMed Central  Google Scholar 

  62. Reeves, G. T. & Stathopoulos, A. Graded dorsal and differential gene regulation in the Drosophila embryo. Cold Spring Harb. Perspect. Biol. 1, a000836 (2009).

    PubMed  PubMed Central  Google Scholar 

  63. 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).

    PubMed  PubMed Central  Google Scholar 

  64. 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  PubMed  Google Scholar 

  65. 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).

    PubMed  Google Scholar 

  66. Lee, J. Y. et al. Wnt/Frizzled signaling controls C. elegans gastrulation by activating actomyosin contractility. Curr. Biol. 16, 1986–1997 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Roh-Johnson, M. et al. Triggering a cell shape change by exploiting preexisting actomyosin contractions. Science 335, 1232–1235 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Marston, D. J. et al. MRCK-1 drives apical constriction in C. elegans by linking developmental patterning to force generation. Curr. Biol. 26, 2079–2089 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Nishimura, T. & Takeichi, M. Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling. Development 135, 1493–1502 (2008).

    CAS  PubMed  Google Scholar 

  70. Haigo, S. L., Hildebrand, J. D., Harland, R. M. & Wallingford, J. B. Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. Curr. Biol. 13, 2125–2137 (2003).

    CAS  PubMed  Google Scholar 

  71. Chung, M. I., Nascone-Yoder, N. M., Grover, S. A., Drysdale, T. A. & Wallingford, J. B. Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut. Development 137, 1339–1349 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Plageman, T. F. Jr. et al. Pax6-dependent Shroom3 expression regulates apical constriction during lens placode invagination. Development 137, 405–415 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Plageman, T. F. Jr. et al. A Trio-RhoA-Shroom3 pathway is required for apical constriction and epithelial invagination. Development 138, 5177–5188 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Ernst, S. et al. Shroom3 is required downstream of FGF signalling to mediate proneuromast assembly in zebrafish. Development 139, 4571–4581 (2012).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  76. Lang, R. A., Herman, K., Reynolds, A. B., Hildebrand, J. D. & Plageman, T. F. Jr. p120-catenin-dependent junctional recruitment of Shroom3 is required for apical constriction during lens pit morphogenesis. Development 141, 3177–3187 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Rauzi, M., Lenne, P. F. & Lecuit, T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature 468, 1110–1114 (2010).

    CAS  PubMed  Google Scholar 

  78. Solon, J., Kaya-Copur, A., Colombelli, J. & Brunner, D. Pulsed forces timed by a ratchet-like mechanism drive directed tissue movement during dorsal closure. Cell 137, 1331–1342 (2009).

    PubMed  Google Scholar 

  79. Munro, E., Nance, J. & Priess, J. R. Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev. Cell 7, 413–424 (2004).

    CAS  PubMed  Google Scholar 

  80. Kim, H. Y. & Davidson, L. A. Punctuated actin contractions during convergent extension and their permissive regulation by the non-canonical Wnt-signaling pathway. J. Cell Sci. 124, 635–646 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Maitre, J. L., Niwayama, R., Turlier, H., Nedelec, F. & Hiiragi, T. Pulsatile cell-autonomous contractility drives compaction in the mouse embryo. Nat. Cell Biol. 17, 849–855 (2015).

    CAS  PubMed  Google Scholar 

  82. Xie, S. & Martin, A. C. Intracellular signalling and intercellular coupling coordinate heterogeneous contractile events to facilitate tissue folding. Nat. Commun. 6, 7161 (2015).

    PubMed  PubMed Central  Google Scholar 

  83. Yevick, H. G., Miller, P. W., Dunkel, J. & Martin, A. C. Structural redundancy in supracellular actomyosin networks enables robust tissue folding. Dev. Cell 50, 586–598 e583 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Bhide, S. et al. Mechanical competition alters the cellular interpretation of an endogenous genetic programme. Preprint at bioRxiv https://doi.org/10.1101/2020.10.15.333963 (2020).

    Article  Google Scholar 

  85. 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).

    CAS  PubMed  Google Scholar 

  86. Llinares-Benadero, C. & Borrell, V. Deconstructing cortical folding: genetic, cellular and mechanical determinants. Nat. Rev. Neurosci. 20, 161–176 (2019).

    CAS  PubMed  Google Scholar 

  87. Garcia, K. E., Kroenke, C. D. & Bayly, P. V. Mechanics of cortical folding: stress, growth and stability. Philos. Trans. R. Soc. Lond. B Biol. Sci. 373, 20170321 (2018).

    PubMed  PubMed Central  Google Scholar 

  88. Huycke, T. R. & Tabin, C. J. Chick midgut morphogenesis. Int. J. Dev. Biol. 62, 109–119 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Walton, K. D., Mishkind, D., Riddle, M. R., Tabin, C. J. & Gumucio, D. L. Blueprint for an intestinal villus: species-specific assembly required. Wiley Interdiscip. Rev. Dev. Biol. 7, e317 (2018).

    PubMed  PubMed Central  Google Scholar 

  90. Vasung, L. et al. Quantitative and qualitative analysis of transient fetal compartments during prenatal human brain development. Front. Neuroanat. 10, 11 (2016).

    PubMed  PubMed Central  Google Scholar 

  91. Neal, J. et al. Insights into the gyrification of developing ferret brain by magnetic resonance imaging. J. Anat. 210, 66–77 (2007).

    PubMed  PubMed Central  Google Scholar 

  92. Lohmann, G., von Cramon, D. Y. & Colchester, A. C. Deep sulcal landmarks provide an organizing framework for human cortical folding. Cereb. Cortex 18, 1415–1420 (2008).

    PubMed  Google Scholar 

  93. Ono, M., Kubik, S. & Abernathey, C. D. Atlas of the Cerebral Sulci (G. Thieme Verlag, 1990).

  94. Mota, B. & Herculano-Houzel, S. Cortical folding scales universally with surface area and thickness, not number of neurons. Science 349, 74–77 (2015).

    CAS  PubMed  Google Scholar 

  95. Van Essen, D. C. A tension-based theory of morphogenesis and compact wiring in the central nervous system. Nature 385, 313–318 (1997).

    PubMed  Google Scholar 

  96. Lefevre, J. & Mangin, J. F. A reaction-diffusion model of human brain development. PLoS Comput. Biol. 6, e1000749 (2010).

    PubMed  PubMed Central  Google Scholar 

  97. Richman, D. P., Stewart, R. M., Hutchinson, J. W. & Caviness, V. S. Jr. Mechanical model of brain convolutional development. Science 189, 18–21 (1975).

    CAS  PubMed  Google Scholar 

  98. Hannezo, E., Prost, J. & Joanny, J. F. Instabilities of monolayered epithelia: shape and structure of villi and crypts. Phys. Rev. Lett. 107, 078104 (2011).

    CAS  PubMed  Google Scholar 

  99. Ben Amar, M. & Jia, F. Anisotropic growth shapes intestinal tissues during embryogenesis. Proc. Natl Acad. Sci. USA 110, 10525–10530 (2013).

    PubMed  Google Scholar 

  100. Mahadevan, L. & Rica, S. Self-organized origami. Science 307, 1740 (2005).

    CAS  PubMed  Google Scholar 

  101. Xu, G. et al. Axons pull on the brain, but tension does not drive cortical folding. J. Biomech. Eng. 132, 071013 (2010).

    PubMed  PubMed Central  Google Scholar 

  102. Tallinen, T., Chung, J. Y., Biggins, J. S. & Mahadevan, L. Gyrification from constrained cortical expansion. Proc. Natl Acad. Sci. USA 111, 12667–12672 (2014).

    CAS  PubMed  Google Scholar 

  103. Tallinen, T. et al. On the growth and form of cortical convolutions. Nat. Phys. 12, 588–593 (2016). Shows that the initial size and geometry of the structure coupled with mechanical instability due to differential tangential growth accounts for the cortical folding pattern observed in fetal human brains. It shows the importance of the initial geometry in positioning folds.

    CAS  Google Scholar 

  104. Kriegstein, A., Noctor, S. & Martinez-Cerdeno, V. Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat. Rev. Neurosci. 7, 883–890 (2006).

    CAS  PubMed  Google Scholar 

  105. Smart, I. H., Dehay, C., Giroud, P., Berland, M. & Kennedy, H. Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb. Cortex 12, 37–53 (2002).

    PubMed  PubMed Central  Google Scholar 

  106. Reillo, I., de Juan Romero, C., Garcia-Cabezas, M. A. & Borrell, V. A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex. Cereb. Cortex 21, 1674–1694 (2011).

    PubMed  Google Scholar 

  107. de Juan Romero, C., Bruder, C., Tomasello, U., Sanz-Anquela, J. M. & Borrell, V. Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly. EMBO J. 34, 1859–1874 (2015).

    PubMed  PubMed Central  Google Scholar 

  108. Savin, T. et al. On the growth and form of the gut. Nature 476, 57–62 (2011). Shows that gut looping arises from growth differences between the gut tube and the anchoring dorsal mesenteric sheet. It documents that equilibrium linear elasticity theory accounts for complex tissue geometry in vivo.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Lyons, K. M., Pelton, R. W. & Hogan, B. L. Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A). Development 109, 833–844 (1990).

    CAS  PubMed  Google Scholar 

  110. Nerurkar, N. L., Mahadevan, L. & Tabin, C. J. BMP signaling controls buckling forces to modulate looping morphogenesis of the gut. Proc. Natl Acad. Sci. USA 114, 2277–2282 (2017).

    CAS  PubMed  Google Scholar 

  111. Coulombre, A. J. & Coulombre, J. L. Intestinal development. I. Morphogenesis of the villi and musculature. J. Embryol. Exp. Morphol. 6, 403–411 (1958).

    CAS  PubMed  Google Scholar 

  112. Shyer, A. E. et al. Villification: how the gut gets its villi. Science 342, 212–218 (2013). Shows that the different steps of avian gut villification result from a mechanical instability due to the expansion of the growing endoderm and the constraints imposed by surrounding muscle layers.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Grey, R. D. Morphogenesis of intestinal villi. I. Scanning electron microscopy of the duodenal epithelium of the developing chick embryo. J. Morphol. 137, 193–213 (1972).

    CAS  PubMed  Google Scholar 

  114. Burgess, D. R. Morphogenesis of intestinal villi. II. Mechanism of formation of previllous ridges. J. Embryol. Exp. Morphol. 34, 723–740 (1975).

    CAS  PubMed  Google Scholar 

  115. Walton, K. D., Freddo, A. M., Wang, S. & Gumucio, D. L. Generation of intestinal surface: an absorbing tale. Development 143, 2261–2272 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Walton, K. D. et al. Villification in the mouse: Bmp signals control intestinal villus patterning. Development 143, 427–436 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Harris, A. K., Stopak, D. & Warner, P. Generation of spatially periodic patterns by a mechanical instability: a mechanical alternative to the Turing model. J. Embryol. Exp. Morphol. 80, 1–20 (1984).

    CAS  PubMed  Google Scholar 

  118. Devenport, D. Tissue morphodynamics: translating planar polarity cues into polarized cell behaviors. Semin. Cell Dev. Biol. 55, 99–110 (2016).

    PubMed  PubMed Central  Google Scholar 

  119. Shindo, A. Models of convergent extension during morphogenesis. Wiley Interdiscip. Rev. Dev. Biol. 7, e293 (2018).

    Google Scholar 

  120. Huebner, R. J. & Wallingford, J. B. Coming to consensus: a unifying model emerges for convergent extension. Dev. Cell 46, 389–396 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Keller, R. & Tibbetts, P. Mediolateral cell intercalation in the dorsal, axial mesoderm of Xenopus laevis. Dev. Biol. 131, 539–549 (1989).

    CAS  PubMed  Google Scholar 

  122. Wilson, P. & Keller, R. Cell rearrangement during gastrulation of Xenopus: direct observation of cultured explants. Development 112, 289–300 (1991).

    CAS  PubMed  Google Scholar 

  123. Shih, J. & Keller, R. Patterns of cell motility in the organizer and dorsal mesoderm of Xenopus laevis. Development 116, 915–930 (1992).

    CAS  PubMed  Google Scholar 

  124. Shih, J. & Keller, R. Cell motility driving mediolateral intercalation in explants of Xenopus laevis. Development 116, 901–914 (1992).

    CAS  PubMed  Google Scholar 

  125. Davidson, L. A., Marsden, M., Keller, R. & Desimone, D. W. Integrin α5β1 and fibronectin regulate polarized cell protrusions required for Xenopus convergence and extension. Curr. Biol. 16, 833–844 (2006).

    CAS  PubMed  Google Scholar 

  126. Skoglund, P., Rolo, A., Chen, X., Gumbiner, B. M. & Keller, R. Convergence and extension at gastrulation require a myosin IIB-dependent cortical actin network. Development 135, 2435–2444 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Munro, E. M. & Odell, G. M. Polarized basolateral cell motility underlies invagination and convergent extension of the ascidian notochord. Development 129, 13–24 (2002).

    CAS  PubMed  Google Scholar 

  128. Williams-Masson, E. M., Heid, P. J., Lavin, C. A. & Hardin, J. The cellular mechanism of epithelial rearrangement during morphogenesis of the Caenorhabditis elegans dorsal hypodermis. Dev. Biol. 204, 263–276 (1998).

    CAS  PubMed  Google Scholar 

  129. Walck-Shannon, E., Reiner, D. & Hardin, J. Polarized Rac-dependent protrusions drive epithelial intercalation in the embryonic epidermis of C. elegans. Development 142, 3549–3560 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Sun, Z. et al. Basolateral protrusion and apical contraction cooperatively drive Drosophila germ-band extension. Nat. Cell Biol. 19, 375–383 (2017).

    CAS  PubMed  Google Scholar 

  131. Williams, M., Yen, W., Lu, X. & Sutherland, A. Distinct apical and basolateral mechanisms drive planar cell polarity-dependent convergent extension of the mouse neural plate. Dev. Cell 29, 34–46 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Irvine, K. D. & Wieschaus, E. Cell intercalation during Drosophila germband extension and its regulation by pair-rule segmentation genes. Development 120, 827–841 (1994).

    CAS  PubMed  Google Scholar 

  133. Bertet, C., Sulak, L. & Lecuit, T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667–671 (2004).

    CAS  PubMed  Google Scholar 

  134. Blankenship, J. T., Backovic, S. T., Sanny, J. S., Weitz, O. & Zallen, J. A. Multicellular rosette formation links planar cell polarity to tissue morphogenesis. Dev. Cell 11, 459–470 (2006). Together with Bertet et al. (2004), shows that cell intercalation during germband extension in D. melanogaster is due to a planar polarized process of cell–cell contact remodelling in which MyoII accumulates at shrinking junctions.

    CAS  PubMed  Google Scholar 

  135. Fernandez-Gonzalez, R. & Zallen, J. A. Oscillatory behaviors and hierarchical assembly of contractile structures in intercalating cells. Phys. Biol. 8, 045005 (2011).

    PubMed  PubMed Central  Google Scholar 

  136. 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).

    CAS  PubMed  Google Scholar 

  137. Yu, J. C. & Fernandez-Gonzalez, R. Local mechanical forces promote polarized junctional assembly and axis elongation in Drosophila. eLife 5, e10757 (2016).

    PubMed  PubMed Central  Google Scholar 

  138. Rauzi, M., Verant, P., Lecuit, T. & Lenne, P. F. Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis. Nat. Cell Biol. 10, 1401–1410 (2008).

    CAS  PubMed  Google Scholar 

  139. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Bambardekar, K., Clement, R., Blanc, O., Chardes, C. & Lenne, P. F. Direct laser manipulation reveals the mechanics of cell contacts in vivo. Proc. Natl Acad. Sci. USA 112, 1416–1421 (2015).

    CAS  PubMed  Google Scholar 

  141. Kale, G. R. et al. Distinct contributions of tensile and shear stress on E-cadherin levels during morphogenesis. Nat. Commun. 9, 5021 (2018).

    PubMed  PubMed Central  Google Scholar 

  142. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Nishimura, T., Honda, H. & Takeichi, M. Planar cell polarity links axes of spatial dynamics in neural-tube closure. Cell 149, 1084–1097 (2012).

    CAS  PubMed  Google Scholar 

  144. Shindo, A. & Wallingford, J. B. PCP and septins compartmentalize cortical actomyosin to direct collective cell movement. Science 343, 649–652 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Shindo, A., Inoue, Y., Kinoshita, M. & Wallingford, J. B. PCP-dependent transcellular regulation of actomyosin oscillation facilitates convergent extension of vertebrate tissue. Dev. Biol. 446, 159–167 (2019).

    CAS  PubMed  Google Scholar 

  146. Zallen, J. A. & Wieschaus, E. Patterned gene expression directs bipolar planar polarity in Drosophila. Dev. Cell 6, 343–355 (2004).

    CAS  PubMed  Google Scholar 

  147. Pare, A. C. et al. A positional Toll receptor code directs convergent extension in Drosophila. Nature 515, 523–527 (2014). Identifies three Toll receptors as downstream targets of pair-rule genes that direct planar polarization in cells of D. melanogaster germband.

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Lavalou, J. et al. Formation of mechanical interfaces by self-organized Toll-8/Cirl GPCR asymmetry. Preprint at bioRxiv https://doi.org/10.1101/2020.03.16.993758 (2020).

    Article  Google Scholar 

  149. Wallingford, J. B. Planar cell polarity and the developmental control of cell behavior in vertebrate embryos. Annu. Rev. Cell Dev. Biol. 28, 627–653 (2012).

    CAS  PubMed  Google Scholar 

  150. Yang, Y. & Mlodzik, M. Wnt-Frizzled/planar cell polarity signaling: cellular orientation by facing the wind (Wnt). Annu. Rev. Cell Dev. Biol. 31, 623–646 (2015).

    PubMed  PubMed Central  Google Scholar 

  151. Butler, M. T. & Wallingford, J. B. Planar cell polarity in development and disease. Nat. Rev. Mol. Cell Biol. 18, 375–388 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Strutt, D. I., Weber, U. & Mlodzik, M. The role of RhoA in tissue polarity and Frizzled signalling. Nature 387, 292–295 (1997).

    CAS  PubMed  Google Scholar 

  153. Winter, C. G. et al. Drosophila Rho-associated kinase (Drok) links Frizzled-mediated planar cell polarity signaling to the actin cytoskeleton. Cell 105, 81–91 (2001).

    CAS  PubMed  Google Scholar 

  154. Andreeva, A. et al. PTK7-Src signaling at epithelial cell contacts mediates spatial organization of actomyosin and planar cell polarity. Dev. Cell 29, 20–33 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Habas, R., Dawid, I. B. & He, X. Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation. Genes Dev. 17, 295–309 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Heisenberg, C. P. et al. Silberblick/Wnt11 mediates convergent extension movements during zebrafish gastrulation. Nature 405, 76–81 (2000).

    CAS  PubMed  Google Scholar 

  157. Wallingford, J. B. et al. Dishevelled controls cell polarity during Xenopus gastrulation. Nature 405, 81–85 (2000).

    CAS  PubMed  Google Scholar 

  158. Keys, D. N., Levine, M., Harland, R. M. & Wallingford, J. B. Control of intercalation is cell-autonomous in the notochord of Ciona intestinalis. Dev. Biol. 246, 329–340 (2002).

    CAS  PubMed  Google Scholar 

  159. Butler, M. T. & Wallingford, J. B. Spatial and temporal analysis of PCP protein dynamics during neural tube closure. eLife 7, e36456 (2018).

    PubMed  PubMed Central  Google Scholar 

  160. Habas, R., Kato, Y. & He, X. Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 107, 843–854 (2001).

    CAS  PubMed  Google Scholar 

  161. Kim, S. K. et al. Planar cell polarity acts through septins to control collective cell movement and ciliogenesis. Science 329, 1337–1340 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Levayer, R. & Lecuit, T. Oscillation and polarity of E-cadherin asymmetries control actomyosin flow patterns during morphogenesis. Dev. Cell 26, 162–175 (2013).

    CAS  PubMed  Google Scholar 

  163. Lye, C. M. et al. Mechanical coupling between endoderm invagination and axis extension in Drosophila. PLoS Biol. 13, e1002292 (2015).

    PubMed  PubMed Central  Google Scholar 

  164. Saadaoui, M., Rocancourt, D., Roussel, J., Corson, F. & Gros, J. A tensile ring drives tissue flows to shape the gastrulating amniote embryo. Science 367, 453–458 (2020).

    CAS  PubMed  Google Scholar 

  165. Aigouy, B. et al. Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 142, 773–786 (2010). Shows that contraction of the hinge region during morphogenesis of the wing in Drosophila mechanically directs cell flows and ultimately orients PCP in the blade region.

    CAS  PubMed  Google Scholar 

  166. Etournay, R. et al. Interplay of cell dynamics and epithelial tension during morphogenesis of the Drosophila pupal wing. eLife 4, e07090 (2015).

    PubMed  PubMed Central  Google Scholar 

  167. Ray, R. P. et al. Patterned anchorage to the apical extracellular matrix defines tissue shape in the developing appendages of Drosophila. Dev. Cell 34, 310–322 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Munster, S. et al. Attachment of the blastoderm to the vitelline envelope affects gastrulation of insects. Nature 568, 395–399 (2019). Shows that blastoderm attachment to the enveloping vitelline membrane orients cellular flows during gastrulation of the beetle Tribolium castaneum, similar to Bailles et al. (2019). Shows the relevance of tissue boundary conditions in directing tissue flows during morphogenesis.

    PubMed  Google Scholar 

  169. Sato, K. et al. Left-right asymmetric cell intercalation drives directional collective cell movement in epithelial morphogenesis. Nat. Commun. 6, 10074 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  170. Coulombre, A. J. The role of intraocular pressure in the development of the chick eye. II. Control of corneal size. AMA Arch. Ophthalmol. 57, 250–253 (1957).

    CAS  PubMed  Google Scholar 

  171. Desmond, M. E. & Jacobson, A. G. Embryonic brain enlargement requires cerebrospinal fluid pressure. Dev. Biol. 57, 188–198 (1977).

    CAS  PubMed  Google Scholar 

  172. Abbas, L. & Whitfield, T. T. Nkcc1 (Slc12a2) is required for the regulation of endolymph volume in the otic vesicle and swim bladder volume in the zebrafish larva. Development 136, 2837–2848 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Navis, A., Marjoram, L. & Bagnat, M. Cftr controls lumen expansion and function of Kupffer’s vesicle in zebrafish. Development 140, 1703–1712 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  174. Ruiz-Herrero, T., Alessandri, K., Gurchenkov, B. V., Nassoy, P. & Mahadevan, L. Organ size control via hydraulically gated oscillations. Development 144, 4422–4427 (2017).

    CAS  PubMed  Google Scholar 

  175. Dasgupta, S., Gupta, K., Zhang, Y., Viasnoff, V. & Prost, J. Physics of lumen growth. Proc. Natl Acad. Sci. USA 115, E4751–E4757 (2018). Quantitatively analyses the contributions of osmotic pressure, cortical tension, cell–cell contact geometry and paracellular leak in the expansion of intercellular lumens.

    CAS  PubMed  Google Scholar 

  176. Chan, C. J. et al. Hydraulic control of mammalian embryo size and cell fate. Nature 571, 112–116 (2019). Shows that feedback between luminal pressure and cortical tension controls the expansion of the mouse blastocysts and affects cell fate specification.

    CAS  PubMed  Google Scholar 

  177. Bryant, D. M. & Mostov, K. E. From cells to organs: building polarized tissue. Nat. Rev. Mol. Cell Biol. 9, 887–901 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  178. Sigurbjornsdottir, S., Mathew, R. & Leptin, M. Molecular mechanisms of de novo lumen formation. Nat. Rev. Mol. Cell Biol. 15, 665–676 (2014).

    PubMed  Google Scholar 

  179. Sperber, I. Secretion of organic anions in the formation of urine and bile. Pharmacol. Rev. 11, 109–134 (1959).

    CAS  PubMed  Google Scholar 

  180. Boyer, J. L. Bile formation and secretion. Compr. Physiol. 3, 1035–1078 (2013).

    PubMed  PubMed Central  Google Scholar 

  181. Navis, A. & Bagnat, M. Developing pressures: fluid forces driving morphogenesis. Curr. Opin. Genet. Dev. 32, 24–30 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Navis, A. & Nelson, C. M. Pulling together: tissue-generated forces that drive lumen morphogenesis. Semin. Cell Dev. Biol. 55, 139–147 (2016).

    PubMed  PubMed Central  Google Scholar 

  183. Mosaliganti, K. R. et al. Size control of the inner ear via hydraulic feedback. eLife 8, e39596 (2019).

    PubMed  PubMed Central  Google Scholar 

  184. Takaoka, K. & Hamada, H. Cell fate decisions and axis determination in the early mouse embryo. Development 139, 3–14 (2012).

    CAS  PubMed  Google Scholar 

  185. Dumortier, J. G. et al. Hydraulic fracturing and active coarsening position the lumen of the mouse blastocyst. Science 365, 465–468 (2019). Illustrates how the formation of blastocoel and the first symmetry breaking event in the mouse embryo depend on a self-organized process of hydraulic fracturing of cell–cell contacts followed by contractility-directed coarsening of microlumens.

    CAS  PubMed  Google Scholar 

  186. Maitre, J. L. et al. Asymmetric division of contractile domains couples cell positioning and fate specification. Nature 536, 344–348 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Samarage, C. R. et al. Cortical tension allocates the first inner cells of the mammalian embryo. Dev. Cell 34, 435–447 (2015).

    CAS  PubMed  Google Scholar 

  188. Plusa, B. et al. Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo. J. Cell Sci. 118, 505–515 (2005).

    CAS  PubMed  Google Scholar 

  189. Nishioka, N. et al. The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev. Cell 16, 398–410 (2009).

    CAS  PubMed  Google Scholar 

  190. Korotkevich, E. et al. The apical domain is required and sufficient for the first lineage segregation in the mouse embryo. Dev. Cell 40, 235–247 e237 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  191. Ryan, A. Q., Chan, C. J., Graner, F. & Hiiragi, T. Lumen expansion facilitates epiblast-primitive endoderm fate specification during mouse blastocyst formation. Dev. Cell 51, 684–697 e684 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Metzger, R. J. & Krasnow, M. A. Genetic control of branching morphogenesis. Science 284, 1635–1639 (1999).

    CAS  PubMed  Google Scholar 

  193. Affolter, M., Zeller, R. & Caussinus, E. Tissue remodelling through branching morphogenesis. Nat. Rev. Mol. Cell Biol. 10, 831–842 (2009).

    CAS  PubMed  Google Scholar 

  194. Ochoa-Espinosa, A. & Affolter, M. Branching morphogenesis: from cells to organs and back. Cold Spring Harb Perspect. Biol. 4, a008243, https://doi.org/10.1101/cshperspect.a008243 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Affolter, M. & Caussinus, E. Tracheal branching morphogenesis in Drosophila: new insights into cell behaviour and organ architecture. Development 135, 2055–2064 (2008).

    CAS  PubMed  Google Scholar 

  196. Sutherland, D., Samakovlis, C. & Krasnow, M. A. branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. Cell 87, 1091–1101 (1996).

    CAS  PubMed  Google Scholar 

  197. Metzger, R. J., Klein, O. D., Martin, G. R. & Krasnow, M. A. The branching programme of mouse lung development. Nature 453, 745–750 (2008). Reveals that the branching pattern of the mouse airways follows stereotypical patterns and sequences and suggests that it reflects the execution of a genetic programme instructing the morphogenesis of branched organs.

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Hannezo, E. et al. A unifying theory of branching morphogenesis. Cell 171, 242–255 e227 (2017). Shows how the stochastic behaviour at the tips of a growing network accounts for several features of branching in the mouse mammary glands and kidney and the human prostate. It shows the relevance of self-organization in the morphogenesis of branched organs.

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Halevi, S. et al. The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors. EMBO J. 21, 1012–1020 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  200. Tsalik, E. L. et al. LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system. Dev. Biol. 263, 81–102 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  201. Dong, X., Liu, O. W., Howell, A. S. & Shen, K. An extracellular adhesion molecule complex patterns dendritic branching and morphogenesis. Cell 155, 296–307 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  202. Salzberg, Y. et al. Skin-derived cues control arborization of sensory dendrites in Caenorhabditis elegans. Cell 155, 308–320 (2013).

    CAS  PubMed  Google Scholar 

  203. Zou, W. et al. A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans. eLife 5, e18345 (2016).

    PubMed  PubMed Central  Google Scholar 

  204. Palavalli, A., Tizón-Escamilla, N., Rupprecht, J.-F. & Lecuit, T. Deterministic and stochastic rules of branching govern dendritic morphogenesis of sensory neurons. Curr. Biol. https://doi.org/10.1016/j.cub.2020.10.054 (2020). Shows that the morphogenesis of the dendritic arbour in a class of sensory neurons in Drosophila embryos results from a combination of deterministic events and self-organizaion.

    Article  PubMed  Google Scholar 

  205. Hashimoto, H., Robin, F. B., Sherrard, K. M. & Munro, E. M. Sequential contraction and exchange of apical junctions drives zippering and neural tube closure in a simple chordate. Dev. Cell 32, 241–255 (2015). Shows that the process of neural tube closure in the chordate Ciona robusta depends on a self-organized cycle of MyoII contraction and neighbour exchange at the front of the zipping wave. Shows the relevance of self-organized processes in moprhogenesis.

    CAS  PubMed  Google Scholar 

  206. Hashimoto, H. & Munro, E. Differential expression of a classic cadherin directs tissue-level contractile asymmetry during neural tube closure. Dev. Cell 51, 158–172 e154 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  207. Munro, E. & Bowerman, B. Cellular symmetry breaking during Caenorhabditis elegans development. Cold Spring Harb. Perspect. Biol. 1, a003400 (2009).

    PubMed  PubMed Central  Google Scholar 

  208. Green, J. B. & Sharpe, J. Positional information and reaction-diffusion: two big ideas in developmental biology combine. Development 142, 1203–1211 (2015).

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank all members of the Lecuit group for stimulating discussions and useful feedback on this manuscript. This review emerged from a lecture series at the Collège de France in 2018. The lab is supported by the ERC grant SelfControl #788308 and the Ligue contre le Cancer. C.C. is supported by the CNRS and T.L. by the Collège de France.

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  1. Aix-Marseille Université & CNRS, IBDM – UMR7288 & Turing Centre for Living Systems, Campus de Luminy Case 907, Marseille, France

    Claudio Collinet & Thomas Lecuit

  2. Collège de France, Paris, France

    Thomas Lecuit

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  1. Claudio Collinet
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Glossary

Denticles

Small cuticular bristles on the ventral side of Drosophila melanogaster larvae that are used for locomotion.

Strain

A measure of deformation of an object with respect to a reference length upon application of a mechanical stress. This is a dimensionless parameter

Reaction–diffusion systems

Mathematical models describing the change in space and time of the concentration of one or more chemical substances. They typically consider local chemical reactions producing or consuming chemical species and their diffusion.

Turing instabilities

A reaction–diffusion system in which the homogeneous equilibrium of mixed chemical substances is unstable owing to random fluctuations and differential diffusion. This gives rise to stationary wave patterns.

Excitable systems

Mechanochemical systems in which positive feedback and delayed negative feedback produce dynamical patterns of activity exhibiting bistability (a stable switch to an on or off state), pulses or oscillations. Spatial coupling mechanisms (for example, diffusion) lead to the emergence of waves of activity as illustrated in the classical example of the action potential.

Morphogenetic fields

Groups of cells responding to discrete, localized biochemical signals leading to the development of specific morphological structures or organs.

Mechanical stress

A physical quantity that expresses the mechanical forces that neighbouring particles of a continuous material exert on each other. It has the dimension of force per surface area (N m−2) or pressure (Pa).

Viscous response

Deformation of a viscous element, which resists shear flow and strain linearly with time when a stress is applied.

Boundary conditions

Constraints defining the limits of a system. In the case of morphogenesis these are typically the physical boundary of a tissue or an embryo.

Lateral line

A sensory system comprising clusters of mechanosensory epithelial cells (neuromasts) arranged as rosettes with their apical surface facing a shared lumen. The lateral line is initially established by a migratory group of cells, called a primordium, that deposits neuromasts at stereotyped locations along the surface of the fish.

Mena/VASP

Members of the VASP (vasodilator-stimulated phosphoprotein) family of proteins regulating the dynamics of the cortical actin cytoskeleton as downstream effectors of the Rho-family small G proteins Rac and Cdc42.

Shroom family proteins

Family of proteins characterized by a specific arrangement of an N-terminal PDZ domain, a central ASD1 (Apx/Shrm Domain 1) motif and a C-terminal ASD2 motif. ASD1 is required for targeting actin, while ASD2 is capable of eliciting an actomyosin constriction event.

Vitelline membrane

Structure surrounding the outer surface of blastoderm cells in embryos of several animals including birds and insects.

Convergence–extension

The process by which a tissue changes shape by narrowing (converging) in one direction and extending along a perpendicular axis.

Traction forces

Forces used to generate motion between a body and a tangential surface, through the use of friction or adhesion. Contractile systems anchored to a rigid body can generate traction forces to move cells or cellular objects.

Notochord

A small flexible rod made from cells from the mesoderm and oriented head to tail in embryos of organisms of the phylum Chordata. As it is composed of stiffer tissue, it allows for skeletal support of the embryo during development.

Germband

Blastoderm tissue corresponding to the ventrolateral region of the embryo in Drosophila melanogaster and other insects.

Primitive streak

Transient structure that forms in the blastula during the early stages of avian, reptilian and mammalian embryonic development. It forms on the dorsal (back) face of the embryo, towards the caudal or posterior end.

Marginal zone

Region corresponding to the equator between the two hemispheres in amphibian embryos.

Pair-rule genes

Group of genes expressed in stripes during segmentation of the embryo in arthropods. In Drosophila pair-rule genes form seven dorsoventrally oriented stripes disposed along the antero-posterior axis.

Toll receptors

A class of single-pass transmembrane receptors involved in patterning and immunity.

Parasegment

The fundamental unit of Drosophila melanogaster development, which is made up of portions of two adjacent segments along the body of the embryo.

Planar cell polarity

The coordinated polarization of a field of cells within the plane of a cell sheet. The axis of planar polarity is typically orthogonal to that of the apico-basal polarity of epithelial cells.

Septins

Cytoskeletal components that upon binding to GTP can polymerize into ordered structures such as rings and filaments, which can function as scaffolds or diffusion barriers.

Advection

The transport of a substance or physical quantity by the movement of the surrounding environment.

Dissipation timescale

Characteristic time at which the internal mechanical stress is reduced by a certain amount by viscous flow.

Bandpass filter

A filter or device that passes frequencies within a certain range and rejects frequencies outside that range.

Epiblast

Also known as primitive ectoderm. One of two distinct layers arising from the inner cell mass in the mammalian blastocyst or the blastodisc in avian and reptile embryos. In mammals, the epiblast sits between the trophectoderm and the hypoblast (or primitive endoderm).

Primitive endoderm

Also known as hypoblast. One of two layers arising from the inner cell mass in the mammalian blastocyst. The primitive endoderm sits between the epiblast and the blastocoel.

PVD neurons

Sensory neurons responding to harsh touch and cold temperatures with a highly elaborate dendritic arborization in the nematode Caenorhabditis elegans.

Vpda class I neurons

Sensory neurons of the peripheral nervous system of Drosophila melanogaster embryos and larvae. The classification is based on the morphology of the dendritic arborization with class I being the simplest morphology and class IV the most complex.

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Collinet, C., Lecuit, T. Programmed and self-organized flow of information during morphogenesis. Nat Rev Mol Cell Biol 22, 245–265 (2021). https://doi.org/10.1038/s41580-020-00318-6

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