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Surface mechanics mediate pattern formation in the developing retina

Abstract

Pattern formation of biological structures involves organizing different types of cells into a spatial configuration. In this study, we investigate the physical basis of biological patterning of the Drosophila retina in vivo. We demonstrate that E- and N-cadherins mediate apical adhesion between retina epithelial cells. Differential expression of N-cadherin within a sub-group of retinal cells (cone cells) causes them to form an overall shape that minimizes their surface contact with surrounding cells. The cells within this group, in both normal and experimentally manipulated conditions, pack together in the same way as soap bubbles do. The shaping of the cone cell group and packing of its components precisely imitate the physical tendency for surfaces to be minimized. Thus, simple patterned expression of N-cadherin results in a complex spatial pattern of cells owing to cellular surface mechanics.

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References

  1. 1

    Etienne-Manneville, S. & Hall, A. Rho GTPases in cell biology. Nature 420, 629–635 (2002)

  2. 2

    Knox, A. L. & Brown, N. H. Rap1 GTPase regulation of adherens junction positioning and cell adhesion. Science 295, 1285–1288 (2002)

  3. 3

    Thompson, D. W. On Growth and Form (Cambridge Univ. Press, Cambridge, 1917)

  4. 4

    Plateau, J. A. F. Statique Experimentale et Theorique des Liquides Soumis aux Seules Forces Moleculaires (Gauthier-Villars, Paris, 1873)

  5. 5

    Taylor, J. E. The structure of singularities in soap-bubble-like and soap-film-like minimal surfaces. Ann. Math. 103, 489–539 (1976)

  6. 6

    Steinberg, M. S. Reconstruction of tissues by dissociated cells: some morphogenetic tissue movements and the sorting out of embryonic cells may have a common explanation. Science 141, 401–408 (1963)

  7. 7

    Steinberg, M. S. & Takeichi, M. Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression. Proc. Natl Acad. Sci. USA 91, 206–209 (1994)

  8. 8

    Foty, R. A., Pfleger, C. M., Forgacs, G. & Steinberg, M. S. Surface tensions of embryonic tissues predict their mutual envelopment behavior. Development 122, 1611–1620 (1996)

  9. 9

    Davis, G. S., Phillips, H. M. & Steinberg, M. S. Germ-layer surface tensions and “tissue affinities” in Rana pipiens gastrulae: quantitative measurements. Dev. Biol. 192, 630–644 (1997)

  10. 10

    Chichilnisky, E. J. A mathematical model of pattern formation. J. Theor. Biol. 123, 81–101 (1986)

  11. 11

    Ready, D. F., Hanson, T. E. & Benzer, S. Development of the Drosophila retina, a neurocrystalline lattice. Dev. Biol. 53, 217–240 (1976)

  12. 12

    Cagan, R. L. & Ready, D. F. The emergence of order in the Drosophila pupal retina. Dev. Biol. 136, 346–362 (1989)

  13. 13

    Wolff, T. & Ready, D. F. in The Development of Drosophila melanogaster (eds Bate, M. & Martinez-Arias, A.) 1277–1325 (Cold Spring Harbor, New York, 1993)

  14. 14

    Strausfeld, N. J. & Nassel, D. R. in Handbook of Sensory Physiology (ed. Autrum, H.) 1–132 (Springer, Berlin, 1981)

  15. 15

    Chanut, F. et al. Rough eye is a gain-of-function allele of amos that disrupts regulation of the proneural gene atonal during Drosophila retinal differentiation. Genetics 160, 623–635 (2002)

  16. 16

    Renfranz, P. J. & Benzer, S. Monoclonal antibody probes discriminate early and late mutant defects in development of the Drosophila retina. Dev. Biol. 136, 411–429 (1989)

  17. 17

    Tepass, U., Tanentzapf, G., Ward, R. & Fehon, R. Epithelial cell polarity and cell junctions in Drosophila. Annu. Rev. Genet. 35, 747–784 (2001)

  18. 18

    Jamora, C. & Fuchs, E. Intercellular adhesion, signalling and the cytoskeleton. Nature Cell Biol. 4, E101–E108 (2002)

  19. 19

    Oda, H., Uemura, T., Harada, Y., Iwai, Y. & Takeichi, M. A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. Dev. Biol. 165, 716–726 (1994)

  20. 20

    Iwai, Y. et al. Axon patterning requires DN-cadherin, a novel neuronal adhesion receptor, in the Drosophila embryonic CNS. Neuron 19, 77–89 (1997)

  21. 21

    Hynes, R. O. & Zhao, Q. The evolution of cell adhesion. J. Cell Biol. 150, 89F–96F (2000)

  22. 22

    Sanson, B., White, P. & Vincent, J. P. Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature 383, 627–630 (1996)

  23. 23

    Zhu, B. et al. Functional analysis of the structural basis of homophilic cadherin adhesion. Biophys. J. 84, 4033–4042 (2003)

  24. 24

    Duguay, D., Foty, R. A. & Steinberg, M. S. Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants. Dev. Biol. 253, 309–323 (2003)

  25. 25

    Bloor, J. W. & Kiehart, D. P. Drosophila RhoA regulates the cytoskeleton and cell-cell adhesion in the developing epidermis. Development 129, 3173–3183 (2002)

  26. 26

    Hayashi, T., Kojima, T. & Saigo, K. Specification of primary pigment cell and outer photoreceptor fates by BarH1 homeobox gene in the developing Drosophila eye. Dev. Biol. 200, 131–145 (1998)

  27. 27

    Peifer, M., Pai, L. M. & Casey, M. Phosphorylation of the Drosophila adherens junction protein Armadillo: roles for wingless signal and zeste-white 3 kinase. Dev. Biol. 166, 543–556 (1994)

  28. 28

    Thomas, G. H. et al. Drosophila β-heavy-spectrin is essential for development and contributes to specific cell fates in the eye. Development 125, 2125–2134 (1998)

  29. 29

    Blochlinger, K., Jan, L. Y. & Jan, Y. N. Postembryonic patterns of expression of cut, a locus regulating sensory organ identity in Drosophila. Development 117, 441–450 (1993)

  30. 30

    Higashijima, S. et al. Dual Bar homeo box genes of Drosophila required in two photoreceptor cells, R1 and R6, and primary pigment cells for normal eye development. Genes Dev. 6, 50–60 (1992)

  31. 31

    Basler, K. & Struhl, G. Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein. Nature 368, 208–214 (1994)

  32. 32

    Godt, D. & Tepass, U. Drosophila oocyte localization is mediated by differential cadherin-based adhesion. Nature 395, 387–391 (1998)

  33. 33

    Pignoni, F. & Zipursky, S. L. Induction of Drosophila eye development by decapentaplegic. Development 124, 271–278 (1997)

  34. 34

    Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22, 451–461 (1999)

  35. 35

    Ito, K., Awano, W., Suzuki, K., Hiromi, Y. & Yamamoto, D. The Drosophila mushroom body is a quadruple structure of clonal units each of which contains a virtually identical set of neurones and glial cells. Development 124, 761–771 (1997)

  36. 36

    Newsome, T. P., Asling, B. & Dickson, B. J. Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development 127, 851–860 (2000)

  37. 37

    Golic, K. G. & Lindquist, S. The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell 59, 499–509 (1989)

  38. 38

    Vincent, J. P. & Lawrence, P. A. Drosophila wingless sustains engrailed expression only in adjoining cells: evidence from mosaic embryos. Cell 77, 909–915 (1994)

  39. 39

    Oda, H. & Tsukita, S. Nonchordate classic cadherins have a structurally and functionally unique domain that is absent from chordate classic cadherins. Dev. Biol. 216, 406–422 (1999)

  40. 40

    Morgan, T. H. Experimental Embryology (Columbia Univ. Press, New York, 1927)

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Acknowledgements

We thank T. Uemura, H. Oda, U. Tepass, G. Thomas, B. Dickson, P. Garrity, the Bloomington Drosophila Stock Center and the Developmental Studies Hybridoma Bank for fly strains and/or antibodies. We also thank K. Saigo for use of facilities. We thank M. Steinberg and R. Matsuda for critical input. We acknowledge G. Beitel, A. Dudley, J. Widom and E. Sontheimer for greatly improving the manuscript. T.H. was supported by a research fellowship from the Japan Society for the Promotion of Science for Young Scientists. This work was also supported by the NIH.

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Correspondence to Takashi Hayashi or Richard W. Carthew.

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The authors declare that they have no competing financial interests.

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Further reading

Figure 1: Pattern formation in different tissues.
Figure 2: Configuration of cone cells precisely correlates with soap bubble configurations.
Figure 3: DE- and DN-cadherins are required for apical adhesion of retinal cells.
Figure 4: DN-cadherin is required for cone cell patterning.
Figure 5: Misexpression of cadherins leads to patterning defects.

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