Katsanos, D;
Koneru, SL;
Boukhibar, LM;
Gritti, N;
Ghose, R;
Appleford, PJ;
Doitsidou, M;
... Barkoulas, M; + view all
(2017)
Stochastic loss and gain of symmetric divisions in the C-elegans epidermis perturbs robustness of stem cell number.
PLoS Biology
, 15
(11)
, Article e2002429. 10.1371/journal.pbio.2002429.
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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.
| Type: | Article |
|---|---|
| Title: | Stochastic loss and gain of symmetric divisions in the C-elegans epidermis perturbs robustness of stem cell number |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pbio.2002429 |
| Publisher version: | http://doi.org/10.1371/journal.pbio.2002429 |
| Language: | English |
| Additional information: | Copyright: © 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. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10071624 |
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