Limits...
Theoretical basis of the community effect in development.

Saka Y, Lhoussaine C, Kuttler C, Ullner E, Thiel M - BMC Syst Biol (2011)

Bottom Line: We have derived the analytical formula for the threshold size of a cell population that is necessary for a community effect, which is in good agreement with stochastic simulation results.The mechanism of the community effect revealed by our theoretical analysis is analogous to that of quorum sensing in bacteria.The community effect may underlie the size control in animal development and also the genesis of autosomal dominant diseases including tumorigenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. y.saka@abdn.ac.uk

ABSTRACT

Background: Genetically identical cells often show significant variation in gene expression profile and behaviour even in the same physiological condition. Notably, embryonic cells destined to the same tissue maintain a uniform transcriptional regulatory state and form a homogeneous cell group. One mechanism to keep the homogeneity within embryonic tissues is the so-called community effect in animal development. The community effect is an interaction among a group of many nearby precursor cells, and is necessary for them to maintain tissue-specific gene expression and differentiate in a coordinated manner. Although it has been shown that the cell-cell communication by a diffusible factor plays a crucial role, it is not immediately obvious why a community effect needs many cells.

Results: In this work, we propose a model of the community effect in development, which consists in a linear gene cascade and cell-cell communication. We examined the properties of the model theoretically using a combination of stochastic and deterministic modelling methods. We have derived the analytical formula for the threshold size of a cell population that is necessary for a community effect, which is in good agreement with stochastic simulation results.

Conclusions: Our theoretical analysis indicates that a simple model with a linear gene cascade and cell-cell communication is sufficient to reproduce the community effect in development. The model explains why a community needs many cells. It suggests that the community's long-term behaviour is independent of the initial induction level, although the initiation of a community effect requires a sufficient amount of inducing signal. The mechanism of the community effect revealed by our theoretical analysis is analogous to that of quorum sensing in bacteria. The community effect may underlie the size control in animal development and also the genesis of autosomal dominant diseases including tumorigenesis.

Show MeSH

Related in: MedlinePlus

Diagram depicting the community effect in development. This figure illustrates the concept of the community effect in an abstract manner. See Introduction for a description of the community effect in muscle development.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3105943&req=5

Figure 1: Diagram depicting the community effect in development. This figure illustrates the concept of the community effect in an abstract manner. See Introduction for a description of the community effect in muscle development.

Mentions: The precursor cells generated by an embryonic induction tend to stay together and form a cell group of like character. Despite the fact that those cells often proliferate and their surrounding environment changes as a consequence of morphogenesis, cells in such a group behave as a collective and express the same set of genes that are unique to their differentiation process. One of the mechanisms that control such collective behaviour of cells during animal development is the so-called community effect [1]. A community effect was first discovered in the muscle precursor cells of Xenopus embryos [2]. Muscle cells are formed from mesoderm, which itself is generated by an inductive interaction of cells in the equatorial region of blastula embryos in Xenopus. Naïve ectoderm cells from blastula embryos change their fate to mesodermal one when juxtaposed to the endodermal tissue that produces the mesoderm-inducing signalling molecules Activin and Xnr (Xenopus nodal-related) proteins. Mesoderm cells that contain muscle precursor cells induced in this way or isolated from early embryos can differentiate into muscle cells when cultured as a group of many cells but not as single cells (Figure 1) [3]. This community effect of many nearby muscle precursor cells requires cell-cell interaction mediated by FGF4 (Fibroblast Growth Factor 4) protein. FGF4 (also known as embryonic FGF or eFGF in Xenopus) is distinct from the mesoderm-inducing signals [4]. FGF4 and the early mesodermal transcription factor Xbra (Xenopus Brachyury) induce expression of each other, thus forming a positive feedback among a group of cells [5,6]. If FGF signalling is blocked by the expression of a dominant negative form of FGF receptor, Xbra expression will be lost [7]. Although it is intuitively apparent that cell-cell communication by diffusible factors plays a crucial role in the community effect, its mechanism is not immediately obvious. Bolouri and Davidson proposed a model of the community effect in sea urchin embryos, which is based on the gene regulatory network operating in the oral ectoderm [8]. In their model, cell-cell communication also plays the central role for the community effect, which is mediated by the Nodal gene product. The basic regulatory unit for a community effect thus seems to be a self-activating feedback loop of a gene that expresses extracellular signalling ligands.


Theoretical basis of the community effect in development.

Saka Y, Lhoussaine C, Kuttler C, Ullner E, Thiel M - BMC Syst Biol (2011)

Diagram depicting the community effect in development. This figure illustrates the concept of the community effect in an abstract manner. See Introduction for a description of the community effect in muscle development.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105943&req=5

Figure 1: Diagram depicting the community effect in development. This figure illustrates the concept of the community effect in an abstract manner. See Introduction for a description of the community effect in muscle development.
Mentions: The precursor cells generated by an embryonic induction tend to stay together and form a cell group of like character. Despite the fact that those cells often proliferate and their surrounding environment changes as a consequence of morphogenesis, cells in such a group behave as a collective and express the same set of genes that are unique to their differentiation process. One of the mechanisms that control such collective behaviour of cells during animal development is the so-called community effect [1]. A community effect was first discovered in the muscle precursor cells of Xenopus embryos [2]. Muscle cells are formed from mesoderm, which itself is generated by an inductive interaction of cells in the equatorial region of blastula embryos in Xenopus. Naïve ectoderm cells from blastula embryos change their fate to mesodermal one when juxtaposed to the endodermal tissue that produces the mesoderm-inducing signalling molecules Activin and Xnr (Xenopus nodal-related) proteins. Mesoderm cells that contain muscle precursor cells induced in this way or isolated from early embryos can differentiate into muscle cells when cultured as a group of many cells but not as single cells (Figure 1) [3]. This community effect of many nearby muscle precursor cells requires cell-cell interaction mediated by FGF4 (Fibroblast Growth Factor 4) protein. FGF4 (also known as embryonic FGF or eFGF in Xenopus) is distinct from the mesoderm-inducing signals [4]. FGF4 and the early mesodermal transcription factor Xbra (Xenopus Brachyury) induce expression of each other, thus forming a positive feedback among a group of cells [5,6]. If FGF signalling is blocked by the expression of a dominant negative form of FGF receptor, Xbra expression will be lost [7]. Although it is intuitively apparent that cell-cell communication by diffusible factors plays a crucial role in the community effect, its mechanism is not immediately obvious. Bolouri and Davidson proposed a model of the community effect in sea urchin embryos, which is based on the gene regulatory network operating in the oral ectoderm [8]. In their model, cell-cell communication also plays the central role for the community effect, which is mediated by the Nodal gene product. The basic regulatory unit for a community effect thus seems to be a self-activating feedback loop of a gene that expresses extracellular signalling ligands.

Bottom Line: We have derived the analytical formula for the threshold size of a cell population that is necessary for a community effect, which is in good agreement with stochastic simulation results.The mechanism of the community effect revealed by our theoretical analysis is analogous to that of quorum sensing in bacteria.The community effect may underlie the size control in animal development and also the genesis of autosomal dominant diseases including tumorigenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. y.saka@abdn.ac.uk

ABSTRACT

Background: Genetically identical cells often show significant variation in gene expression profile and behaviour even in the same physiological condition. Notably, embryonic cells destined to the same tissue maintain a uniform transcriptional regulatory state and form a homogeneous cell group. One mechanism to keep the homogeneity within embryonic tissues is the so-called community effect in animal development. The community effect is an interaction among a group of many nearby precursor cells, and is necessary for them to maintain tissue-specific gene expression and differentiate in a coordinated manner. Although it has been shown that the cell-cell communication by a diffusible factor plays a crucial role, it is not immediately obvious why a community effect needs many cells.

Results: In this work, we propose a model of the community effect in development, which consists in a linear gene cascade and cell-cell communication. We examined the properties of the model theoretically using a combination of stochastic and deterministic modelling methods. We have derived the analytical formula for the threshold size of a cell population that is necessary for a community effect, which is in good agreement with stochastic simulation results.

Conclusions: Our theoretical analysis indicates that a simple model with a linear gene cascade and cell-cell communication is sufficient to reproduce the community effect in development. The model explains why a community needs many cells. It suggests that the community's long-term behaviour is independent of the initial induction level, although the initiation of a community effect requires a sufficient amount of inducing signal. The mechanism of the community effect revealed by our theoretical analysis is analogous to that of quorum sensing in bacteria. The community effect may underlie the size control in animal development and also the genesis of autosomal dominant diseases including tumorigenesis.

Show MeSH
Related in: MedlinePlus