Delay models for the early embryonic cell cycle oscillator

PLoS One. 2018 Mar 26;13(3):e0194769. doi: 10.1371/journal.pone.0194769. eCollection 2018.

Abstract

Time delays are known to play a crucial role in generating biological oscillations. The early embryonic cell cycle in the frog Xenopus laevis is one such example. Although various mathematical models of this oscillating system exist, it is not clear how to best model the required time delay. Here, we study a simple cell cycle model that produces oscillations due to the presence of an ultrasensitive, time-delayed negative feedback loop. We implement the time delay in three qualitatively different ways, using a fixed time delay, a distribution of time delays, and a delay that is state-dependent. We analyze the dynamics in all cases, and we use experimental observations to interpret our results and put constraints on unknown parameters. In doing so, we find that different implementations of the time delay can have a large impact on the resulting oscillations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism
  • Animals
  • Biological Clocks
  • CDC2 Protein Kinase / metabolism
  • Cell Cycle
  • Embryo, Nonmammalian / cytology
  • Models, Biological*
  • Xenopus Proteins / metabolism
  • Xenopus laevis / growth & development
  • Xenopus laevis / physiology*
  • Zygote / cytology
  • Zygote / metabolism
  • cdc25 Phosphatases / metabolism

Substances

  • Xenopus Proteins
  • Anaphase-Promoting Complex-Cyclosome
  • CDC2 Protein Kinase
  • cdc25 Phosphatases

Grants and funding

The authors acknowledge support by the Research-Foundation Flanders (FWO-Vlaanderen) for individual support (J.R.) and project support (L.G. - grant G0A5217N). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.