Abstract
Sensory neuron numbers and positions are precisely organized to accurately map environmental signals in the brain. This precision emerges from biochemical processes within and between cells that are inherently stochastic. We investigated impact of stochastic gene expression on pattern formation, focusing on senseless (sens), a key determinant of sensory fate in Drosophila. Perturbing microRNA regulation or genomic location of sens produced distinct noise signatures. Noise was greatly enhanced when both sens alleles were present in homologous loci such that each allele was regulated in trans by the other allele. This led to disordered patterning. In contrast, loss of microRNA repression of sens increased protein abundance but not sensory pattern disorder. This suggests that gene expression stochasticity is a critical feature that must be constrained during development to allow rapid yet accurate cell fate resolution.
Highlights
The irreversible progression from a disordered to an ordered arrangement of cells within tissues is a hallmark of development
An outstanding challenge is to determine whether stochasticity inherent to gene expression is transmitted across scales to vary the fidelity of pattern formation
We have focused on the organization of sensory bristles along the adult wing margin
Summary
The irreversible progression from a disordered to an ordered arrangement of cells within tissues is a hallmark of development. The proneural proteins co-activate their own transcription within each cell (Acar et al, 2006; JafarNejad et al, 2003; Jafar-Nejad et al, 2006; Nolo et al, 2000) These interlinked positive feedback loops ensure that initially small differences in proneural protein abundance between neighboring cells evolve into large differences (Figure 1C). Since lateral inhibition harnesses the variation in proneural protein abundance, we have sought to understand if stochasticity in proneural gene expression is filtered out by spatial signal integration between cells; or transmitted across scales to disrupt ordered sensory bristle patterning. We find that stochastic features of Sens protein expression are greatly enhanced when one sens allele influences the expression of its paired homolog in trans When this occurs, cells in the proneural stripes experience abnormally high noise in Sens protein output, which resolves by lateral inhibition into a disordered pattern of sensory bristles. Cis versus trans modes of gene regulation can have major effects on the regularity of sensory pattern formation
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