, Volume 9, Issue 3, pp 365–382 | Cite as

Semiotic Tools For Multilevel Cell Communication

  • Franco GiorgiEmail author
  • Gennaro Auletta


Cell communication plays a key role in multicellular organisms. In developing embryos as in adult organisms, cells communicate by coordinating their differentiation through the establishment and/or renewal of a variety of cell communication channels. Under both these conditions, cells interact by either receptor signalling, surface recognition of specific cell adhesion molecules or transfer of cytoplasmic components through junctional coupling. In recent years, it has become apparent that cells may also communicate through the extracellular release of microvesicles. They may originate as either exosomes from the endosomal compartment upon fusion of multivesicular bodies with the plasma membrane or be shed directly from the plasma membrane via extensions of the cell surface. Microvesicles may disperse over long distances through body fluids and deliver their molecular cargo onto a variety of target cells. As a general rule, the metabolic fate of these cells is determined by the molecular nature of the vesicular cargo, while targeting itself depends on the affinity of the molecules expressed on the enclosing membrane. In this paper, we will be arguing that intercellular vesicular transfer is substantially different from other types of cell communication, allowing cells and molecules to interact on varying levels. Cells interacting via ligand signalling owe their specificity to the steric coupling with cognate receptor molecules. As such, it is a pure molecular process that affects target cells only upon integration into their responding repertoire. In this relationship, coupled cells are reciprocally adapted to each other through the selection of their respective signalling capacities, following exploration of their receptor specificity. Interaction by intercellular vesicles realizes a substantially different type of cell communication. Vesicular traffic allows donor cells to carry out a horizontal type of gene transfer and target this information over long distances via independently controlled mechanisms. Because of this independence, cells interacting via vesicular traffic are not expected to adapt their signalling correspondences, but to control instead the efficiency of their cargo delivery irrespective of the receptor repertoire expressed by the target tissue. In this paper, the multifaceted functions of the intercellular vesicular traffic will be discussed in a multilevel biosemiotic perspective with the aim of unravelling the cellular mechanisms devised by nature to accomplish communication.


Microvesicles Semiosis Multilevel Selection Scaffolding 


  1. Agapakis, C. M., Boyle, P. M., & Silver, P. A. (2012). Natural strategies for the spatial optimization of metabolism in synthetic biology. Nature Chemical Biology, 8, 527–535.CrossRefPubMedGoogle Scholar
  2. Ashe, H. L., & Briscoe, J. (2006). The interpretation of morphogen gradients. Development, 133, 385–394.CrossRefPubMedGoogle Scholar
  3. Auletta, G. (2011). Cognitive Biology: Dealing with Information from bacteria to minds. Oxford University Press.Google Scholar
  4. Auletta, G. (2015). Emergence: selection, allowed operations, and conserved quantities. South-African. Journal of Philosophy, 34, 93–105.Google Scholar
  5. Auletta, G., Ellis, G., & Jaeger, L. (2008). Top-Down causation by information control: From a philosophical problem to a scientific research program. Journal of the Royal Society: Interface, 5, 1159–1172.PubMedCentralGoogle Scholar
  6. Ayala, S. J. (1994). Transport and internal organization of membranes: vesicles, membrane networks and GTP-binding proteins. Journal of Cell Science, 107, 753–763.PubMedGoogle Scholar
  7. Bains, P. (2014). The primacy of semiosis. An ontology of relations. Toronto: University of Toronto Press.Google Scholar
  8. Barabási, A. L. (2007). The architecture of complexity. IEEE Control Systems Magazine, 27(4), 33–42.CrossRefGoogle Scholar
  9. Barabási, A.-L., & Oltvai, Z. N. (2004). Network biology: understanding the cell’s functional organization. Nature Reviews Genetics, 5, 101–113.CrossRefPubMedGoogle Scholar
  10. Baum, W. M. (2004). Molar and molecular views of choice. Behavioural Processes, 66(3), 349–359.CrossRefPubMedGoogle Scholar
  11. Bennett, M.V.L. (2009). Gap junctions and electrical synapses. In: Squire, L.R. (ed.). Encyclopedia of Neuroscience, 4, (pp. 529–548). Oxford: Academic Press.Google Scholar
  12. Bongrand, P. (1999). Ligand-receptor interactions. Progress in Physics, 62, 921–968.CrossRefGoogle Scholar
  13. Brasset, E., Taddei, A. R., Arnaud, F., Faye, B., Fausto, A. M., Mazzini, M., Giorgi, F., & Vaury, C. (2006). Viral particles of the endogenous retrovirus ZAM from Drosophila melanogaster use a pre-existing endosome/exosome pathway for transfer to the oocyte. Retrovirology, 3, 25.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Brawand, D., Wahli, W., & Kaessmann, H. (2008). Loss of egg yolk genes in mammals and the origin of lactation and placentation. PLoS Biology, 6(3), e63.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Bruni, L. E., & Giorgi, F. (2015). Towards a heterarchical approach to biology and cognition. Progress in Biophysics and Molecular Biology, 119, 481–492.CrossRefPubMedGoogle Scholar
  16. Camussi, G., Deregibus, M. C., Bruno, S., Cantaluppi, V., & Biancone, L. (2010). Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney International, 78, 838–848.CrossRefPubMedGoogle Scholar
  17. Cariani, P. (1998). Towards an evolutionary semiotics: the emergence of new sign-functions in organisms and devices. In: Van De Vijver, G., Salthe, S., and Delpos M. (eds.). Evolutionary Systems. Biological and Epistemological Perspectives on Selection and Self-Organization. (pp. 359–377). Kluwer Academic Publishers Dordrecht, Holland.Google Scholar
  18. Chanson, M., Derouette, J. P., Roth, I., Foglia, B., Scerri, I., Dudez, T., & Kwak, B. R. (2005). Gap junctional communication in tissue inflammation and repair. Biochimica Biophysica Acta, 1711(2), 197–207.CrossRefGoogle Scholar
  19. Cocucci, E., & Meldolesi, J. (2015). Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends in Cell Biology, 25, 364–372.CrossRefPubMedGoogle Scholar
  20. Cocucci, E., Racchetti, G., & Meldolesi, J. (2009). Shedding microvesicles: artefacts no more. Trends in Cell Biology, 19, 43–51.CrossRefPubMedGoogle Scholar
  21. Corrado, C., Raimondo, S., Chiesi, A., Ciccia, F., De Leo, G., & Alessandro, R. (2013). Exosomes as intercellular signalling organelles involved in health and disease: Basic science and clinical applications. International Journal of Molecular Sciences, 14, 5338–5366.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Crescitelli, R., Lässer, C., Szabó, T. G., Kittel, A., Eldh, M., Dianzani, I., Buzás, E. I., & Lötvall, J. (2013). Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. Journal of Extracellular Vesicles, 2, 20677.CrossRefGoogle Scholar
  23. Deacon, T. W. (2012). Incomplete Nature. New York: How mind emerged from matter. Norton WW & Company.Google Scholar
  24. Deatherage, B. L., & Cookson, B. T. (2012). Membrane vesicle release in Bacteria, Eukaryotes, and Archaea: A conserved yet underappreciated aspect of microbial life. Infection and Immunity, 80, 1948–1957.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Dehmelt, L., & Bastiaens, L. I. H. (2010). Spatial organization of intracellular communication: Insights from imaging. Nature Reviews Molecular Cell Biology, 11, 440–452.CrossRefPubMedGoogle Scholar
  26. DiMario, P. J., & Mahowald, A. E. (1987). Female sterile (1) yolkless: A recessive female sterile mutation in Drosophila melanogaster with depressed numbers of coated pits and coated vesicles within the developing oocytes. The Journal of Cell Biology, 105, 199–206.CrossRefPubMedGoogle Scholar
  27. Dolezal, P., Likic, V., Tachezy, J., & Lithgow, T. (2006). Evolution of the molecular machines for protein import into mitochondria. Science, 313, 314–318.CrossRefPubMedGoogle Scholar
  28. Edman, K., Hosseini, A., Bjursell, M. K., Aagaard, A., Wissler, L., Gunnarsson, A., Kaminski, T., Köhler, C., Bäckström, S., Jensen, T. J., Cavallin, A., Karlsson, U., Nilsson, E., Lecina, D., Takahashi, R., Grebner, C., Geschwindner, S., Lepistö, M., Hogner, A. C., & Guallar, V. (2015). Ligand binding mechanism in steroid receptors: From conserved plasticity to differential evolutionary constraints. Structure, 23(12), 2280–2290.CrossRefPubMedGoogle Scholar
  29. Ek-Vitorin, J. F., & Burt, J. M. (2013). Structural basis for the selective permeability of channels made of communicating junction proteins. Biochimica Biophysica Acta, 1828(1), 51–68.CrossRefGoogle Scholar
  30. Emmeche, C., Queiroz, J., & El-Hani, C. (2010). Information and Semiosis in Living Systems: A Semiotic Approach. In D. Favareau (Ed.), ). Essential Readings in Biosemiotics, vol. 3. (pp. 629–656). Dondrect: Springer.Google Scholar
  31. Estelles, A., Sperinde, J., Roulon, T., Aguilar, B., Bonner, C., LePecq, J.-B., & Delcayre, A. (2007). Exosome nanovesicles displaying G protein coupled receptors for drug discovery. International Journal of Nanomedicine, 2(4), 751–760.PubMedPubMedCentralGoogle Scholar
  32. Giorgi, F., & Bruni, L. E. (2015). Developmental scaffolding. Biosemiotics, 8, 173–189.CrossRefGoogle Scholar
  33. Giorgi, F., Bruni, L. E., & Maggio, R. (2010). Receptor oligomerization as a process modulating cellular semiotics. Biosemiotics, 3, 157–176.CrossRefGoogle Scholar
  34. Goldberg, G.S., Valiunas, V., & Brink, P.R. (2004). Selective permeability of gap junction channels Biochimica Biophysica Acta, 1662, 96–101.Google Scholar
  35. Gould, S. J., & Raposo, G. (2013). As we wait: Coping with an imperfect nomenclature for extracellular vesicles. Journal of Extracellular Vesicles, 2, 20389.CrossRefGoogle Scholar
  36. Gross, J. C., Chaudhary, V., K., B., & Boutros, M. (2012). Active Wnt proteins are secreted on exosomes. Nature Cell Biology, 14(10), 1036–1045.CrossRefPubMedGoogle Scholar
  37. György, B., Szabó, T. G., Pásztói, M., Pál, Z., Misják, P., Aradi, B., László, V., Pállinger, E., Pap, E., Kittel, A., Nagy, G., Falus, A., & Buzás, E. I. (2011). Membrane vesicles, current state-of-the-art: Emerging role of extracellular vesicles. Cellular and Molecular Life Sciences, 68(16), 2667–2688.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Haga, H., Yan, I. K., Takahashi, K., Wood, J., Zubair, A., & Patel, T. (2015). Tumour cell-derived extracellular vesicles interact with mesenchymal stem cells to modulate the microenvironment and enhance cholangiocarcinoma growth. Journal of Extracellular Vesicles, 4, 24900.CrossRefPubMedGoogle Scholar
  39. Hakulinen, J., Sankkila, L., Sugiyama, N., Lehti, K., & Keski-Oja, J. (2008). Secretion of active membrane type 1 matrix metalloproteinase (MMP-14) into extracellular space in microvesicular exosomes. Journal of Cell Biochemistry, 105(5), 1211–1218.CrossRefGoogle Scholar
  40. Harries-Jones, P. (2016). Upside-down Gods. Gregory Bateson’s world of difference: Fordham University Press, New York.CrossRefGoogle Scholar
  41. Hodgins, M.B. (2004). Connecting wounds with connexins. Journal Investigative Dermatology, 122, ix–x.Google Scholar
  42. Hoffmeyer, J. (1998). Surfaces inside surfaces – On the origin of agency and life. Cybernetics and Human Knowing, 5(1), 33–42.Google Scholar
  43. Hoffmeyer, J. (2010). A biosemiotic approach to the question of meaning. Zygon, 45(2), 367–390.CrossRefGoogle Scholar
  44. Hu, G., Drescher, K. M., & Chen, X.-M. (2012). Exosomal miRNAs: Biological properties and therapeutic potential. Frontiers in Genetics, 3, 56.PubMedPubMedCentralGoogle Scholar
  45. Ilina, O., & Friedl, P. (2009). Mechanisms of collective cell migration at a glance. Journal of Cell Science, 122, 3203–3208.CrossRefPubMedGoogle Scholar
  46. Kanczuga-Koda, L., Koda, M., Sulkowski, S., Wincewicz, A., Zalewski, B., & Sulkowska, M. (2010). Gradual loss of functional gap junction within progression of colorectal cancer - a shift from membranous CX32 and CX43 expression to cytoplasmic pattern during colorectal carcinogenesis. In Vivo, 24(1), 101–107.PubMedGoogle Scholar
  47. Kholodenko, B. N. (2006). Cell signalling dynamics in time and space. Nature Review on. Molecular Cell Biology, 7(3), 165–176.PubMedPubMedCentralGoogle Scholar
  48. Kim, K. M., & Caetano-Anolle’s, G. (2010). Emergence and evolution of modern molecular functions inferred from phylogenomic analysis of ontological data. Molecular Biology and Evolution, 27(7), 1710–1733.CrossRefPubMedGoogle Scholar
  49. Kooijmans, S. A. A., Vader, P., van Dommelen, S. M., van Solinge, W. W., & Schiffelers, R. M. (2012). Exosome mimetics: a novel class of drug delivery systems. International Journal of Nanomedicine, 7, 1525–1541.PubMedPubMedCentralGoogle Scholar
  50. Kotini, M., & Mayor, R. (2015). Connexins in migration during development and cancer. Developmental Biology, 401(1), 143–151.CrossRefPubMedGoogle Scholar
  51. Kull, K. (1999). Biosemiotics in the twentieth century: a view from biology. Semiotica, 127, 385–414.Google Scholar
  52. Laghezza Masci, V., Taddei, A. R., Gambellini, G., Giorgi, F., & Fausto, A. M. (2016). Ultrastructural investigation on fibroblast interaction with collagen scaffold. Journal of Biomedical Material Research, 104(1), 272–282.CrossRefGoogle Scholar
  53. Lamouille, S., Xu, J., & Derynck, R. (2014). Molecular mechanisms of epithelial–mesenchymal transition. Nature Reviews Molecular Cell Biology, 15, 178–196.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Lauffenburger, D. A., Oehrtman, G. T., Walker, L., & Wiley, H. S. (1998). Real-time quantitative measurement of autocrine ligand binding indicates that autocrine loops are spatially localized. Proceedings of the National Academy of Sciences USA, 95(26), 15368–15373.CrossRefGoogle Scholar
  55. Leblanc, P., Desset, S., Giorgi, F., Taddei, A. R., Fausto, A. M., Mazzini, M., Dastugue, B., & Vaury, C. (2000). Life Cycle of an Endogenous Retrovirus, ZAM, in Drosophila melanogaster. Journal of Virology, 74, 10658–10669.CrossRefPubMedPubMedCentralGoogle Scholar
  56. Levin, M. (2007). Gap junctional communication in morphogenesis. Progress in Biophysics and Molecular Biology, 94(1-2), 186–206.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Lin, Y., Meng, Y., Wang, Y. X., Luo, J., Katsuma, S., Yang, C. W., Banno, Y., Kusakabe, T., Shimada, T., & Xia, Q. Y. (2013). Vitellogenin receptor mutation leads to the oogenesis mutant phenotype “scanty vitellin” of the silkworm, Bombyx mori. Journal Biological Chemistry, 288(19), 13345–13355.CrossRefGoogle Scholar
  58. Maran, T., & Kleisner, K. (2010). Towards an evolutionary biosemiotics: Semiotic selection and semiotic co-option. Biosemiotics, 3(2), 189–200.CrossRefGoogle Scholar
  59. Marquez-Rosado, L., Singh, D., Rincon-Arano, H., Solan, J. L., & Lampe, P. D. (2012). CASK (LIN2) interacts with Cx43 in wounded skin and their coexpression affects cell migration. Journal of Cell Science, 125, 695–702.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Martínez, A. D., Acuña, R., Figueroa, V., Maripillan, J., & Nicholson, B. (2009). Gap-junction channels dysfunction in deafness and hearing loss. Antioxidants & Redox Signaling, 11(2), 309–322.CrossRefGoogle Scholar
  61. McCarthy, N. (2010). Cell signalling: regulation and crosstalk. Nature Reviews Molecular Cell Biology, 11, 390.CrossRefPubMedGoogle Scholar
  62. Meckes Jr., D. G. (2015). Exosomal communication goes viral. Journal of Virology, 89, 5200–5203.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Meckes Jr., D. G., & Raab-Traub, N. (2011). Microvesicles and viral Infection. Journal of Virology, 85, 12844–12854.CrossRefPubMedPubMedCentralGoogle Scholar
  64. Morré, D. J., & Mollenhauer, H. H. (1974). The endomembrane concept: A functional integration of endoplasmic reticulum and Golgi apparatus. In A. W. Robards (Ed.), Dynamic Aspects of Plant infrastructure (pp. 84–137). London, New York: McGraw-Hill.Google Scholar
  65. Morré, D. J., & Mollenhauer, H. H. (2007). Microscopic morphology and the origins of the membrane maturation model of Golgi apparatus function. International Review of Cytology, 262, 191–218.CrossRefGoogle Scholar
  66. Mulcahy, L. A., Pink, R. C., & Carter, D. R. F. (2014). Routes and mechanisms of extracellular vesicle uptake. Journal of Extracellular Vesicles, 3, 24641.Google Scholar
  67. Müller, G. (2012). Novel tools for the study of cell type-specific exosomes and microvesicles. Journal of Bioanalysis & Biomedicine, 4, 46–60.Google Scholar
  68. Muralidharan-Chari, V., Clancy, J. W., Sedgwick, A., & D’Souza-Schorey, C. (2010). Microvesicles: Mediators of extracellular communication during cancer progression. Journal of Cell Sciences,, 123, 1603–1611.CrossRefGoogle Scholar
  69. Nawaz, M., Fatima, F., Zanetti, B. R., de Lima Martins, I., Schiavotelo, N. L., Mendes, N. D., Nacasaki Silvestre, R., & Neder, L. (2014). Microvesicles in gliomas and medulloblastomas: An overview. Journal of Cancer Therapy, 5, 182–191.CrossRefGoogle Scholar
  70. Niklas, K. J. (2014). The evolutionary-developmental origins of multicellularity. American Journal of Botany, 101(1), 6–25.CrossRefPubMedGoogle Scholar
  71. Nolte-‘t Hoen, E. N., Buschow, S. I., Anderton, S. M., Stoorvogel, W., & Wauben, M. H. (2009). Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood, 113, 1977–1981.CrossRefPubMedGoogle Scholar
  72. Nowack, D. D., Morré, D. M., Paulik, M., Keenan, T. W., & Morré, D. J. (1987). Intracellular membrane flow: reconstitution of transition vesicle formation and function in a cell-free system. Proceedings of the National Academy of Sciences, USA, 84(17), 6098–6102.CrossRefGoogle Scholar
  73. Nussey, S., & Whitehead, S. (2001). Endocrinology. An Integrated Approach. Oxford: BIOS Scientific Publishers.CrossRefGoogle Scholar
  74. Pattee, H. H. (2001). The physics of symbols: bridging the epistemic cut. Bio Systems, 60, 5–21.CrossRefPubMedGoogle Scholar
  75. Pattee, H. H., & Kull, K. (2009). A biosemiotic conversation: Between physics and semiotics. Sign Systems Studies, 37(1/2), 311–331.Google Scholar
  76. Pattee, H. H., & Raczaszek-Leonardi, J. (2012). Law, language and life. Biosemiotics vol 7. Dondrecht: Springer.CrossRefGoogle Scholar
  77. Peters, C., & von Figura, K. (1994). Biogenesis of lysosomal membranes. FEBS Letters, 346, 108–114.CrossRefPubMedGoogle Scholar
  78. Postlethwait, J. H., & Giorgi, F. (1985). Vitellogenesis in insects. In L. W. Browder (Ed.), Developmental Biology. A comprehensive Synthesis. Oogenesis (pp. 85–119). New York and London: Plenum Press.Google Scholar
  79. Queiroz, J., & El-Hani, C. N. (2006). Semiosis as an emergent process. Transactions of the Charles S. Peirce Society: A Quarterly Journal in American Philosophy, 42, 78–116.CrossRefGoogle Scholar
  80. Raikhel, A. S., & Dhadialla, T. S. (1992). Accumulation of yolk proteins in insect oocytes. Annual Review of Entomology, 37, 217–251.CrossRefPubMedGoogle Scholar
  81. Raikhel, A. S., Brown, M., & Belles, X. (2005). Endocrine control of reproductive processes. In L. Gilbert, G. S., & I. Iatrou (Eds.), Comprehensive Molecular Insect Science. Vol. 3 (pp. 433–491). Endocrinology: Elsevier Press.CrossRefGoogle Scholar
  82. Raposo, G., & Stoorvogel, W. (2013). Extracellular vesicles: Exosomes, microvesicles, and friends. Journal of Cell Biology, 200, 373–383.CrossRefPubMedPubMedCentralGoogle Scholar
  83. Robertson, J. D. (1981). Membrane structure. The Journal of Cell Biology, 91, 189 s–204 s.CrossRefGoogle Scholar
  84. Robinson, R. (2008). For mammals, loss of yolk and gain of milk went hand in hand. PLoS Biology, 6, e77.CrossRefPubMedPubMedCentralGoogle Scholar
  85. Schaffer, S. W., & Suleiman, M.-S. (2007). Mitochondria. The dynamic organelle. New York: Springer.CrossRefGoogle Scholar
  86. Schlosser, G., & Wagner, G. P. (2004). Modularity in development and evolution. Chicago and London: The University of Chicago Press.Google Scholar
  87. Segura, E., Guerin, C., Hogg, N., Amigorena, S., & Thery, C. (2007). CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. Journal of Immunology, 179, 1489–1496.CrossRefGoogle Scholar
  88. Sharov, A. A. (2014). Evolutionary constraints or opportunities? BioSystems, 120, 21–30.CrossRefGoogle Scholar
  89. Uings, I. J., & Farrow, S. N. (2000). Cell receptors and cell signalling. Journal of Clinical Pathology, 53, 295–299.Google Scholar
  90. Vachias, C., Fritsch, C., Pouchin, P., Bardot, O., & Mirouse, V. (2014). Tight coordination of growth and differentiation between germline and soma provides robustness for Drosophila egg development. Cell Reports, 9(2), 531–541.CrossRefPubMedGoogle Scholar
  91. van der Grein, S. G., & Nolte-'t Hoen, E. N. (2014). “Small Talk” in the innate immune system via RNA-containing extracellular vesicles. Frontiers in Immunology, 5, 542.PubMedPubMedCentralGoogle Scholar
  92. van der Meel, R., Fens, M., Vader, P., van Solinge, W. W., Eniola-Adefeso, O., & Schiffelers, R. M. (2014). Extracellular vesicles as drug delivery systems: Lessons from the liposome field. Journal of Controlled Release, 195, 72–85.CrossRefPubMedGoogle Scholar
  93. Vella, L. J., Sharples, R. A., Lawson, V. A., Masters, C. L., Cappai, R., & Hill, A. F. (2007). Packaging of prions into exosomes is associated with a novel pathway of PrP processing. Journal of Pathology, 211, 582–590.CrossRefPubMedGoogle Scholar
  94. Vleminckx, K. (2001). Adhesive specificity and the evolution of multicellularity. Encyclopedia of Life Sciences. (pp. 1–8). Nature Publishing Group.Google Scholar
  95. Wagner, A. (2008). Robustness and evolvability: a paradox resolved. Proceedings of the Royal Society of London B, 275, 91–100.CrossRefGoogle Scholar
  96. Wallace, R. A. (1985). Vitellogenesis and oocyte growth in nonmammalian vertebrates. In L. W. Browder (Ed.), Developmental Biology. A comprehensive Synthesis. Oogenesis (pp. 127–166). New York and London: Plenum Press.Google Scholar
  97. Wang, Z., & Zhang, J. (2009). Abundant Indispensable Redundancies in Cellular Metabolic Networks. Genome Biology and Evolution, 1, 23–33.CrossRefPubMedPubMedCentralGoogle Scholar
  98. Wendler, F., Bota-Rabassedas, N., & Franch-Marro, X. (2013). Cancer becomes wasteful: Emerging roles of exosomes in cell-fate determination. Journal of Extracellular Vesicles, 2, 22390.CrossRefGoogle Scholar
  99. Woodward, J. (2003). Making things happen. A theory of causal explanation. Oxford: Oxford University Press.Google Scholar
  100. Wurdinger, T., Gatson, N. N., Balaj, L., Kaur, B., Breakefield, X. O., & Pegtel, D. M. (2012). Extracellular vesicles and their convergence with viral pathways. Advances in Virology, 2012, 767694.CrossRefPubMedPubMedCentralGoogle Scholar
  101. Xu, J., & Nicholson, B. J. (2013). The role of connexins in ear and skin physiology - functional insights from disease-associated mutations. Biochimica Biophysica Acta, 1828(1), 167–178.CrossRefGoogle Scholar
  102. Yáñez-Mó, M., et al. (2015). Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4, 27066.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media Dordrecht 2016

Authors and Affiliations

  1. 1.University of PisaPisaItaly
  2. 2.University of CassinoCassinoItaly

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