A role for the fusogen eff-1 in epidermal stem cell number robustness in Caenorhabditis elegans

Sneha L Koneru,Michalis Barkoulas,Nicola Gritti,Jeroen Sebastiaan van Zon,Mark Hintze,Ritobrata Ghose,Fu Xiang Quah

doi:10.1038/s41598-021-88500-4

Abstract

Developmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. We focus here on a population of epidermal cells, the seam cells, which show stem cell-like behaviour and divide symmetrically and asymmetrically over post-embryonic development to generate epidermal and neuronal tissues. We have conducted a mutagenesis screen to identify mutants that introduce phenotypic variability in the normally invariant seam cell population. We report here that a null mutation in the fusogen eff-1 increases seam cell number variability. Using time-lapse microscopy and single molecule fluorescence hybridisation, we find that seam cell division and differentiation patterns are mostly unperturbed in eff-1 mutants, indicating that cell fusion is uncoupled from the cell differentiation programme. Nevertheless, seam cell losses due to the inappropriate differentiation of both daughter cells following division, as well as seam cell gains through symmetric divisions towards the seam cell fate were observed at low frequency. We show that these stochastic errors likely arise through accumulation of defects interrupting the continuity of the seam and changing seam cell shape, highlighting the role of tissue homeostasis in suppressing phenotypic variability during development.

Highlights

Developmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise
We investigate here how phenotypic variability emerges in the C. elegans epidermis and report that eff-1 lossof-function mutants display an increase in seam cell number variability
We were interested in identifying mutants that showed an increase in seam cell number variance without a change in the mean, which would be indicative of developmental variability introduced within the isogenic population (Fig. 1b)

Summary

Introduction

Developmental patterning in Caenorhabditis elegans is known to proceed in a highly stereotypical manner, which raises the question of how developmental robustness is achieved despite the inevitable stochastic noise. The C. elegans L1 larvae are born with 10 seam cells per lateral side These cells undergo stereotypical symmetric and asymmetric cell divisions during larval development. Asymmetric cell divisions are reiterative throughout development, and the most common case involves an anterior daughter cell that differentiates into a neuron or epidermal cell, while the posterior daughter retains the seam cell fate. These division and differentiation patterns give rise to 16 seam cells per lateral side in wild-type animals at the end of larval development, a number which is robust in standard growth conditions, it can be sensitive to temperature increase[9,10]. The developmental fate that these epidermal cells acquire when fusion fails is still not well understood[15,21]

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Conclusion