A cell fate switch in theC. elegansseam cell lineage occurs through modulation of the Wnt asymmetry pathway in response to temperature increase

Abstract

23Populations often display consistent developmental phenotypes across individuals 24 despite the inevitable biological stochasticity. Nevertheless, developmental robustness 25 has limits and systems can fail upon change in the environment or the genetic 26 background. We use here the seam cells, a population of epidermal stem cells in 27 Caenorhabditis elegans, to study the influence of temperature change and genetic 28 variation on cell fate. Seam cell development has mostly been studied so far in the lab 29 reference strain (N2), grown at 20° temperature. We demonstrate that an increase in 30 culture temperature to 25°, introduces variability in the wild-type seam cell lineage with a 31 proportion of animals showing an increase in seam cell number. We map this increase to 32 lineage-specific symmetrisation events of normally asymmetric cell divisions at the final 33 larval stage, leading to the retention of seam cell fate in both daughter cells. Using 34 genetics and single molecule imaging, we demonstrate that this symmetrisation occurs 35 via changes in the Wnt asymmetry pathway, leading to aberrant Wnt target activation in 36 anterior cell daughters. We find that intrinsic differences in the Wnt asymmetry pathway 37 already exist between seam cells at 20° and this may sensitise cells towards a cell fate 38 switch at increased temperature. Finally, we demonstrate that wild isolates of C. elegans 39 display variation in seam cell sensitivity to increased culture temperature, although seam 40 cell numbers are comparable when raised at 20°. Our results highlight how temperature 41 can modulate cell fate decisions in an invertebrate model of stem cell patterning. 42 43 44 45 46 47 48 During development, organisms must withstand environmental and genetic perturbations 49 to produce consistent phenotypes (Felix and Barkoulas 2012). These phenotypes are 50 often a product of complex developmental events that require a tight balance between cell 51 division and cell differentiation (Soufi and Dalton 2016). A key example is stem cell 52 divisions, consisting of highly controlled asymmetric and symmetric patterns, which are 53 vital for generating cell diversity, as well as maintaining cell numbers in tissues and organs 54 (Morrison and Kimble 2006; Knoblich 2008). Developmental robustness has inherent 55 limits and certain perturbations can push a system outside its buffering zone (Braendle 56 and Felix 2008; Barkoulas et al. 2013). In these cases, it is also important to understand 57 how systems fail by investigating how perturbations precisely modulate developmental 58 processes. Here we address the question of how changes in environmental temperature 59 can affect cell fate outcomes using the nematode C. elegans as a model system. While it 60 is well known that increasing or decreasing environmental temperature can change the 61 development speed in C. elegans, the effect of temperature on specific cell division and 62 fate acquisition events is less well understood. The C. elegans adult hermaphrodite 63 co...