It is essential that correct temporal order of cellular events is maintained during animal development. During postembryonic 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 unique time-lapse microscopy approach to simultaneously measure timing of oscillatory gene expression, hypodermal stem cell divisions, and cuticle shedding in individual Caenorhabditis elegans larvae, as they developed 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 total duration of development in each individual. We also observed pervasive changes in timing when temperature, diet, or genotype were varied, but with larval development divided in “epochs” that differed in how event timing was impacted. Yet, these variations in timing were still explained by temporal scaling when time 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. However, shifting conditions middevelopment perturbed temporal scaling and changed event order in a highly condition-specific manner, indicating that a complex machinery is responsible for temporal scaling under constant conditions.

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European Union Horizon 2020 , NWO VIDI
Quantitative Developmental Biology

Filina, O., Demirbas, B., Haagmans, R., & van Zon, J. (2022). Temporal scaling in C. elegans larval development. PNAS, 119(11). doi:10.1073/pnas.2123110119