Cooperative differentiation through clustering in multicellular populations

Aneta Koseska, Ekkehard Ullner, Evgenii Volkov, Jurgen Kurths, Jordi García-Ojalvo

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95 Citations (Scopus)


The coordinated development of multicellular organisms is driven by intercellular communication. Differentiation into diverse cell types is usually associated with the existence of distinct attractors of gene regulatory networks, but how these attractors emerge from cell–cell coupling is still an open question. In order to understand and characterize the mechanisms through which coexisting attractors arise in multicellular systems, here we systematically investigate the dynamical behavior of a population of synthetic genetic oscillators coupled by chemical means. Using bifurcation analysis and numerical simulations, we identify various attractors and attempt to deduce from these findings a way to predict the organized collective behavior of growing populations. Our results show that dynamical clustering is a generic property of multicellular systems. We argue that such clustering might provide a basis for functional differentiation and variability in biological systems.
Original languageEnglish
Pages (from-to)189-202
Number of pages14
JournalJournal of Theoretical Biology
Issue number2
Early online date22 Nov 2009
Publication statusPublished - 21 Mar 2010

Bibliographical note

A.K. and J.K. acknowledge the GoFORSYS project funded by the Federal Ministry of Education and Research, Grant no. 0313924, E.U. acknowledges financial support from SULSA, Deutsche Forschungsgemeinschaft (SFB 618) and the Alexander von Humboldt Foundation, E.V. the Program “Radiofizika” Russian Academy and RFBR Grant nos. 08-0200682, 08-0100131, J.G.O. the Ministerio de Ciencia e Innovacion (Spain) (Project FIS2009-13360 and I3 program) and J.K. the EU through the Network of Excellence BioSim, Contract no. LSHB-CT-2004-005137. This work has also been supported by the European Commission (Project GABA, FP6-NEST Contract 043309).


  • multicellular systems
  • clustering
  • collective behavior
  • inhibitory cell-to-cell communication
  • cellular differentiation


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