Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number.
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens.
Date Issued
2017-11-06
Date Acceptance
2017-10-20
Citation
PLoS Biology, 2017, 15 (11)
ISSN
1544-9173
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Biology
Volume
15
Issue
11
Copyright Statement
© 2017 Katsanos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
PII: pbio.2002429
Subjects
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Developmental Biology
Publication Status
Published online
Article Number
e2002429