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bioRxiv · 10.1101/2021.03.24.436858

A folder mechanism ensures size uniformity among C. elegans individuals by coupling growth and development

Towbin, B. D.·Grosshans, H.
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Abstract

Animals increase by orders of magnitude in their volume during development. Hence, even small differences in the growth rates between individuals could generate large differences in their adult body size. Yet, such volume divergence among individuals is usually not observed in nature. We combined theory and experiment to understand the mechanisms of body size uniformity. Using live imaging, we measured the volume growth of hundreds of individuals of C. elegans over the entire span of their postembryonic development. We find that C. elegans grows exponentially in volume with a coefficient of variation of the growth rate of [~]7%, but that individuals diverge much less in volume than expected from this heterogeneity. The mechanism counteracting size divergence does not involve size thresholds for developmental milestones. Instead, an inverse coupling of the growth rate and the duration of development produces a constant volume fold change per larval stage. The duration of larval stages of C. elegans is determined by the period of a developmental oscillator. Using mathematical modelling, we show that an anti-correlation between the growth rate and the oscillatory period emerges as an intrinsic property of a genetic oscillator. We propose that the robustness of body volume fold change is a hard-wired characteristic of the oscillatory circuit and does not require elaborate mechanisms of size control by cellular signalling. Indeed, the coupling of growth and development was unaltered by mutation of canonical pathways of growth control. This novel concept of size homeostasis may broadly apply to other multicellular systems controlled by genetic oscillators.

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Towbin, B. D., Grosshans, H.. 2021-03-25. A folder mechanism ensures size uniformity among C. elegans individuals by coupling growth and development. https://doi.org/10.1101/2021.03.24.436858

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