Filtering transcriptional noise during development: concepts and mechanisms

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Abstract
Transcriptional noise is a natural consequence of the molecular interactions that mediate gene expression. 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). 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. 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. 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. 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. We suggest that the filtering of transcriptional noise during development requires targeted chromatin remodelling and that Wnt signalling is dedicated to this function.