University of Bern, Bern, Switzerland.
Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland.
Nat Commun. 2022 Jun 6;13(1):3132. doi: 10.1038/s41467-022-29720-8.
Animals increase by orders of magnitude in volume during development. Therefore, small variations in growth rates among individuals could amplify to a large heterogeneity in size. By live imaging of C. elegans, we show that amplification of size heterogeneity is prevented by an inverse coupling of the volume growth rate to the duration of larval stages and does not involve strict size thresholds for larval moulting. We perturb this coupling by changing the developmental tempo through manipulation of a transcriptional oscillator that controls the duration of larval development. As predicted by a mathematical model, this perturbation alters the body volume. Model analysis shows that an inverse relation between the period length and the growth rate is an intrinsic property of genetic oscillators and can occur independently of additional complex regulation. This property of genetic oscillators suggests a parsimonious mechanism that counteracts the amplification of size differences among individuals during development.
动物在发育过程中体积呈数量级增长。因此,个体间生长速度的微小差异可能会导致体型的巨大异质性。通过对秀丽隐杆线虫的活体成像,我们发现通过体积生长率与幼虫阶段持续时间的反向耦合,可以防止体型异质性的放大,并且幼虫蜕皮不需要严格的大小阈值。我们通过操纵控制幼虫发育持续时间的转录振荡器来改变发育节奏,从而干扰这种耦合。正如数学模型所预测的,这种干扰会改变身体体积。模型分析表明,周期长度与生长率之间的反比关系是遗传振荡器的固有特性,并且可以独立于其他复杂的调节发生。遗传振荡器的这一特性表明,有一种简单的机制可以抵消发育过程中个体间体型差异的放大。