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

Abstract
Data availability
Article and author information
Metrics

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.

Data availability

All data generated and analyzed during this study are included in the manuscript and supporting files. Source data is provided for all main figures and computer code for analysis and modeling are available at https://github.com/ritika-giri/stochastic-noise.

The following previously published data sets were used

(2017) Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo
NCBI Gene Expression Omnibus, GSE100370.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE100370
1. Shah PK
2. Kheradpour P
3. Morrison CA
4. Henikoff JG
5. Feng X
6. Ahmad K
7. Russell S
8. White RAH et al
(2010) A comprehensive map of insulator elements for the Drosophila genome
NCBI Gene Expression Omnibus, GSE16245.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16245
1. Li X
2. MacArthur S
3. Bourgon R
4. Nix D
5. Pollard DA
6. Iyer VN
7. Hechmer A
8. Simirenko L
9. Stapleton M
10. Hendriks CLL et al
(2008) ranscription factors bind thousands of active and inactive regions in the Drosophila blastoderm
NCBI PLoS Biology, Table S2.

https://doi.org/10.1371/journal.pbio.0060027.st002

Article and author information

Author details

Ritika Giri

Department of Molecular Biosciences, Northwestern University, Evanston, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8838-0818
Dimitrios K Papadopoulos

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Diana M Posadas

Department of Molecular Biosciences, Northwestern University, Evanston, United States

Competing interests
The authors declare that no competing interests exist.
Hemanth K Potluri

Department of Molecular Biosciences, Northwestern University, Evanston, United States

Competing interests
The authors declare that no competing interests exist.
Pavel Tomancak

Max Planck Institute of Cell Biology and Genetics, Dresden, Germany

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2222-9370
Madhav Mani

Engineering Sciences and Applied Mathematics, Northwestern University, Evanston, United States

For correspondence
madhav.mani@northwestern.edu

Competing interests
The authors declare that no competing interests exist.
Richard W Carthew

Department of Molecular Biosciences, Northwestern University, Evanston, United States

For correspondence
r-carthew@northwestern.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0343-0156

Funding

National Institutes of Health (R35GM118144)

Ritika Giri
Diana M Posadas
Hemanth K Potluri
Richard W Carthew

Simons Foundation (597491)

Madhav Mani
Richard W Carthew

National Science Foundation (1764421)

Madhav Mani
Richard W Carthew

Pew Charitable Trusts (Pew Latin American Fellows Program)

Diana M Posadas

Max Planck Society (MPI Funding)

Dimitrios K Papadopoulos
Pavel Tomancak

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.