Key Points
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Transcriptional noise is a natural consequence of the molecular interactions that mediate gene expression.
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Experimental evidence has recently begun to emerge on the molecular basis of transcriptional noise in prokaryotes and lower eukaryotes. This work has allowed a detailed analysis of this variable and its influence on the performance of simple gene-regulatory networks (GRNs).
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The development and patterning of an organism relies on the coordination of the expression of many genes over many cells. Extrapolation of the findings that are derived from the analysis of noise in simple systems indicates the potential for chaotic behaviour in developmental GRNs.
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The performance of GRNs is robust and reproducible; this indicates that dedicated mechanisms exist to control and reduce the noise that is associated with the performance of developmental GRNs.
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Cell-fate assignations are a fundamental element of developmental systems and can be represented as a transition between cell states — from S1 to S2. At some point during this transition cells are in a noisy, undefined state (that is, they are in the S1/S2 state). The transition from S1 to S1/S2 reflects the induction of gene expression that is associated with S2, whereas the transition from S1/S2 to S2 represents the stabilization of the S2 gene-expression pattern.
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Wnt signalling does not seem to be involved in the induction of patterns of gene expression during development but rather in their stabilization. As such, Wnt signalling acts as a noise filter.
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We suggest that the filtering of transcriptional noise during development requires targeted chromatin remodelling and that Wnt signalling is dedicated to this function.
Abstract
The assignation of cell fates during eukaryotic development relies on the coordinated and stable expression of cohorts of genes within cell populations. The precise and reproducible nature of this process is remarkable given that, at the single-cell level, the transcription of individual genes is associated with noise — random molecular fluctuations that create variability in the levels of gene expression within a cell population. Here we consider the implications of transcriptional noise for development and suggest the existence of molecular devices that are dedicated to filtering noise. On the basis of existing evidence, we propose that one such mechanism might depend on the Wnt signalling pathway.
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Acknowledgements
We would like to thank U.-M. Fiuza, M. Gonzalez-Gaitan, M. Isalan, J. Gurdon, T. Kouzarides, V. Morel, P. Sanders and L. Serrano for comments on the manuscript. Special thanks to H. Bolouri and A. Friday for tutorials and discussions on subjects of which we would otherwise have been unaware. The research of the authors is supported by The Wellcome Trust.
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Glossary
- Cell state
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The molecular phenotype of a cell. At the transcriptional level, it is defined by the profile of gene expression that defines its phenotype. It can refer to a terminally differentiated cell or to one that is at a certain stage of development.
- Non-Markovian sequence
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A sequence of events in which a given step depends exclusively on the position of the system and not on its history. One example is the fate of adult stem cells, which can be coaxed to differentiate into any cell type independently of their history.
- Morphogen
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A signalling molecule that elicits sensitive concentration-dependent responses in gene expression.
- Gene-regulatory networks
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Functionally significant arrangements of regulatory interactions between individual genes that carry out specific information-processing tasks.
- Fidelity
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The reliability with which a process is executed; the degree of reliability between the input and output of a pathway or network.
- Transfer function
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A parameter that measures the relationship between the input and output in a network.
- Endomesoderm
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The group of cells that give rise to the endoderm and mesoderm.
- Network motifs
-
Stereotyped patterns of interactions between the basic regulatory elements of a network in bacteria and yeast. They are defined as the functional interactions between the elements of a network that occur in real networks more than other possible interactions.
- Bistability
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The observation that for a certain range of parameters the system can exist in either of two (or many — multistability) stable states.
- Induction
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The definition of a particular and molecularly defined state through an input.
- Syncitium
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A multinucleate cell in which the nuclei are not separated by cell membranes.
- Lateral inhibition
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A developmental strategy that curtails the development of a particular fate in cells that surround a cell that has already adopted this fate.
- Community effect
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A developmental strategy that results in the development of homogeneous and stable expression levels of a particular gene or genes across a population that initially had low and variable expression levels of those genes.
- Competence domain
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A group of cells that share the potential to adopt a particular fate.
- Transdetermination
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The property of cells to spontaneously change their commitment from one particular developmental trajectory to another.
- Imaginal disc
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A specialized groups of cells in Diptera that give rise to adult structures such as wings or eyes. They are set aside during embryogenesis, proliferate inside the larva and then produce the adult structures during pupation.
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Arias, A., Hayward, P. Filtering transcriptional noise during development: concepts and mechanisms. Nat Rev Genet 7, 34–44 (2006). https://doi.org/10.1038/nrg1750
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DOI: https://doi.org/10.1038/nrg1750
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