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Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number.

Authors :
Dimitris Katsanos
Sneha L Koneru
Lamia Mestek Boukhibar
Nicola Gritti
Ritobrata Ghose
Peter J Appleford
Maria Doitsidou
Alison Woollard
Jeroen S van Zon
Richard J Poole
Michalis Barkoulas
Source :
PLoS Biology, Vol 15, Iss 11, p e2002429 (2017)
Publication Year :
2017
Publisher :
Public Library of Science (PLoS), 2017.

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.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
15449173 and 15457885
Volume :
15
Issue :
11
Database :
Directory of Open Access Journals
Journal :
PLoS Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.6277508cb47d427395d2628aabc8f068
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pbio.2002429