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

  1. Ritika Giri
  2. Dimitrios K Papadopoulos
  3. Diana M Posadas
  4. Hemanth K Potluri
  5. Pavel Tomancak
  6. Madhav Mani  Is a corresponding author
  7. Richard W Carthew  Is a corresponding author
  1. Northwestern University, United States
  2. University of Edinburgh, United Kingdom
  3. Max Planck Institute of Cell Biology and Genetics, Germany

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

Article and author information

Author details

  1. Ritika Giri

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8838-0818
  2. 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.
  3. Diana M Posadas

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hemanth K Potluri

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Pavel Tomancak

    Max Planck Institute of Cell Biology and Genetics, Dresden, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2222-9370
  6. 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.
  7. 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.
    ORCID icon "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.

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: November 15, 2019
  2. Accepted: February 25, 2020
  3. Accepted Manuscript published: February 26, 2020 (version 1)
  4. Version of Record published: March 10, 2020 (version 2)

Copyright

© 2020, Giri et al.

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.

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  1. Ritika Giri
  2. Dimitrios K Papadopoulos
  3. Diana M Posadas
  4. Hemanth K Potluri
  5. Pavel Tomancak
  6. Madhav Mani
  7. Richard W Carthew
(2020)
Ordered patterning of the sensory system is susceptible to stochastic features of gene expression
eLife 9:e53638.
https://doi.org/10.7554/eLife.53638

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