Imperial College London


Faculty of Natural SciencesDepartment of Life Sciences

Senior Lecturer



+44 (0)20 7594 5227m.barkoulas




607Sir Alexander Fleming BuildingSouth Kensington Campus






BibTex format

author = {Katsanos, D and Koneru, SL and Mestek, Boukhibar L and Gritti, N and Ghose, R and Appleford, PJ and Doitsidou, M and Woollard, A and van, Zon JS and Poole, RJ and Barkoulas, M},
doi = {10.1371/journal.pbio.2002429},
journal = {PLoS Biology},
title = {Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number.},
url = {},
volume = {15},
year = {2017}

RIS format (EndNote, RefMan)

AB - 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.
AU - Katsanos,D
AU - Koneru,SL
AU - Mestek,Boukhibar L
AU - Gritti,N
AU - Ghose,R
AU - Appleford,PJ
AU - Doitsidou,M
AU - Woollard,A
AU - van,Zon JS
AU - Poole,RJ
AU - Barkoulas,M
DO - 10.1371/journal.pbio.2002429
PY - 2017///
SN - 1544-9173
TI - Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number.
T2 - PLoS Biology
UR -
UR -
VL - 15
ER -