Ordered patterning of the sensory system is susceptible to stochastic features of gene expression

Ritika Giri; Dimitrios K. Papadopoulos; Diana M. Posadas; Hemanth K. Potluri; Pavel Tomancak; Madhav Mani; Richard W. Carthew

doi:10.7554/eLife.53638

Ordered patterning of the sensory system is susceptible to stochastic features of gene expression

Ritika Giri, Dimitrios K. Papadopoulos, Diana M. Posadas, Hemanth K. Potluri, Pavel Tomancak, Madhav Mani, Richard W. Carthew^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	e53638
Journal	eLife
Volume	9
DOIs	https://doi.org/10.7554/eLife.53638
State	Published - Feb 2020

Funding

Fly stocks from Hugo Bellen and the Bloomington Drosophila Stock Center are gratefully appreciated. Antibodies were gifts from Hugo Bellen and purchases from the Developmental Studies Hybridoma Bank. We thank Koen Venken for extensive help with BAC recombineering protocols and reagents. We thank Michael Stadler and Michael Eisen for generously providing HiC maps of the 22A3 and 57F5 loci from their studies. We thank Jessica Hornick and the Biological Imaging Facility for help with imaging. Financial support was provided from the Northwestern Data Science Initiative (R.G.), Robert H. Lurie Comprehensive Cancer Center (R.G.), Pew Latin American Fellows Program (D.M.P.), Max Planck Society (D.K.P. and P.T.), Chancellor’s Fellowship of University of Edinburgh (D.K.P.), NIH (R35GM118144, R.W.C.), NSF (1764421, M.M and R.W.C.), and the Simons Foundation (597491, M.M. and R.W.C.). M.M. is a Simons Foundation Investigator.

ASJC Scopus subject areas

General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology
General Neuroscience

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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.",

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Ordered patterning of the sensory system is susceptible to stochastic features of gene expression

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