Temporal scaling in C. elegans larval development

Abstract It is essential that correct temporal order of cellular events is maintained during animal development. During post-embryonic development, the rate of development depends on external conditions, such as food availability, diet and temperature. How timing of cellular events is impacted when the rate of development is changed at the organism-level is not known. We used a novel time-lapse microscopy approach to simultaneously measure timing of oscillatory gene expression, hypodermal stem cell divisions and cuticle shedding in individual animals, during C. elegans larval development from hatching to adulthood. This revealed strong variability in timing between isogenic individuals under the same conditions. However, this variability obeyed ‘temporal scaling’, meaning that events occurred at the same time when measured relative to the duration of development in each individual. We also observed pervasive changes in population-averaged timing when temperature, diet or genotype were varied, but with larval development divided in ‘epochs’ that differed in how the timing of events was impacted. Yet, these variations in timing were still explained by temporal scaling when timing was rescaled by the duration of the respective epochs in each individual. Surprisingly, timing obeyed temporal scaling even in mutants lacking lin-42/Period , presumed a core regulator of timing of larval development, that exhibited strongly delayed, heterogeneous timing and growth arrest. Timing of larval development is likely controlled by timers based on protein degradation or protein oscillations, but such mechanisms do not inherently generate temporal scaling. Hence, our observations will put strong constraints on models to explain timing of larval development.