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About the Authors:
Dimitris Katsanos
Roles Formal analysis, Investigation, Methodology, Writing - original draft, Writing - review & editing
Affiliation: Department of Life Sciences, Imperial College, London, United Kingdom
Sneha L. Koneru
Roles Formal analysis, Investigation, Methodology, Writing - original draft, Writing - review & editing
Affiliation: Department of Life Sciences, Imperial College, London, United Kingdom
Lamia Mestek Boukhibar
Roles Investigation
Current address: Centre for Translational Omics-GOSgene, Genetics and Genomic Medicine, University College London, Institute of Child Health, London, United Kingdom
Affiliation: Department of Life Sciences, Imperial College, London, United Kingdom
Nicola Gritti
Roles Formal analysis, Investigation, Methodology
Affiliation: Institute for Atomic and Molecular Physics (AMOLF), Amsterdam, The Netherlands
Ritobrata Ghose
Roles Investigation, Methodology
Affiliation: Department of Life Sciences, Imperial College, London, United Kingdom
Peter J. Appleford
Roles Investigation, Methodology, Resources
Affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom
Maria Doitsidou
Roles Investigation, Resources, Writing - review & editing
Affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom
Alison Woollard
Roles Investigation, Resources
Affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom
Jeroen S. van Zon
Roles Formal analysis, Investigation, Methodology
Affiliation: Institute for Atomic and Molecular Physics (AMOLF), Amsterdam, The Netherlands
Richard J. Poole
Roles Formal analysis, Investigation, Methodology, Resources, Writing - review & editing
Affiliation: Department of Cell and Developmental Biology, University College London, London, United Kingdom
Michalis Barkoulas
Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Supervision, Writing - original draft, Writing - review & editing
* E-mail: [email protected]
Affiliation: Department of Life Sciences, Imperial College, London, United Kingdom
ORCID http://orcid.org/0000-0003-1974-7668Abstract
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...