Sensitivity to perturbations of a cell migration under temporal regulation

Few studies have measured the robustness to perturbations of the final position of a long-range migrating cell. In the nematode Caenorhabditis elegans, the QR neuroblast migrates anteriorly in the young larva, while undergoing three rounds of division. The daughters of QR.pa stop their migration at an anterior body position and acquire a neuronal fate. Previous studies showed that the migration stops upon expression of the Wnt receptor MIG-1, which surprisingly is not induced by positional cues but by a timing mechanism (Mentink et al. 2014). Given this temporal regulation, we wondered 1) how precise QR.pax positioning is when confronted with various challenges, such as stochastic noise, environment or body size variation and 2) whether QR.pax position varies among C. elegans wild isolates. We find that the variance of QR.pax final position is similar to that of other long-range migrating neurons. Its mean position undergoes a slight posterior shift at higher temperature, while its variance is greatly increased following sustained starvation at hatching. We manipulated body size using mutants and tetraploid animals. As expected from the temporal mechanism, smaller mutants display anteriorly shifted QR.pax cells, while longer mutants and tetraploids display posteriorly shifted QR.pax cells. Using a mathematical model, we show however that body size variation is partially compensated. We find that cell speed is indeed altered in body size mutants. Finally, we could detect highly significant variation among C. elegans wild isolates. Overall, this study reveals that the final cell position of QR.pax shows some degree of sensitivity to external perturbations and natural genetic variation.