Affiliations: Lille University, Laboratoire d'Informatique Fondamentale de Lille (LIFL, CNRS UMR 8022), Cite Scientifique, Batiment M3, 59655 Villeneuve d'Ascq CEDEX, France, [email protected] | University of Aberdeen, School of Medical Sciences, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK
Note: [] Address for correspondence: LIFL, Lille University I, France
Note: [] KB's PhD project is co-funded by CNRS and the Conseil Régional Nord-Pas de Calais. CK and CL are supported by Lille 1 University and the Agence Nationale de Recherche through a Jeunes Chercheurs grant (ANR BioSpace, 2009-2011), and for this grant's duration, KB, CK, and CL were hosted within the Interdisciplinary Research Institute of Lille (CNRS USR 3078).
Note: [] YS's work is supported by SULSA (Scottish Universities Life Science Alliances) and the University of Aberdeen.
Abstract: For decades, scientists have sought to elucidate self-organized patterning during development of higher organisms. It has been shown that cell interaction plays a key role in this process. One example is the community effect, an interaction among undifferentiated cells. The community effect allows cell population to forge a common identity, that is, coordinated and sustained tissue-specific gene expression. The community effect was originally observed in muscle differentiation in Xenopus embryos, and is now thought to be a widespread phenomenon. From a modelling point of view, the community effect is the existence of a threshold size of cell populations, above which the probability of tissue-specific gene expression for a sustained period increases significantly. Below this threshold size, the cell population fails to maintain tissue-specific gene expression after the initial induction. In this work, we examine the dynamics of a community effect in space and investigate its roles in two other processes of self-organized patterning by diffusible factors: Turing's reaction-diffusion system and embryonic induction by morphogens. Our major results are the following. First, we show that, starting from a one-dimensional space model with the simplest possible feedback loop, a community effect spreads in an unlimited manner in space. Second, this unrestricted expansion of a community effect can be avoided by additional negative feedback. In Turing's reaction-diffusion system with a built-in community effect, if induction is localized, sustained activation also remains localized. Third, when a simple cross-repression gene circuitry is combined with a community effect loop, the system self-organizes. A gene expression pattern with a well-demarcated boundary appears in response to a transient morphogen gradient. Surprisingly, even when the morphogen distribution eventually becomes uniform, the system can maintain the pattern. The regulatory network thus confers memory of morphogen dynamics.
