An endogenous calcium oscillator may control early embryonic division.
Transient elevations in the concentration of free cytosolic calcium ion ([Ca2+]i) promote cell phase transitions in early embryonic division and persist even if these transitions are blocked. These observations suggest that a [Ca2+]i oscillator is an essential timing element of the early embryonic "master clock." We explore this possibility by coupling a [Ca2+]i oscillator model to an early embryonic cell cycle model based on the protein interactions that govern the activity of the M-phase-promoting factor (MPF). We hypothesize three dynamical states of the MPF system and choose parameter sets to represent each. We then investigate how [Ca2+]i dynamics may control early embryonic division in both sea urchin and Xenopus embryos. To investigate both systems, distinct [Ca2+]i profiles matching those observed in sea urchin embryos (in which [Ca2+]i exhibits sharp transients) and Xenopus embryos (in which [Ca2+]i is elevated and oscillates sinusoidally) are imposed on each of the hypothesized dynamical states of MPF. In the first hypothesis, [Ca2+]i oscillations entrain the autonomous MPF oscillator. In the second and third hypotheses, where the MPF system rests in excitatory and bistable states, respectively, [Ca2+]i oscillations drive MPF activation cycles. Simulation results show that hypotheses two and three, in which a [Ca2+]i oscillator is a fundamental timing element of the master clock, best account for key experimental observations and the questions that they raise. Finally, we propose experiments to elucidate further [Ca2+]i regulation and the fundamental components of the early embryonic master clock.
Swanson
C A
CA
Department of Chemistry, Stanford University, CA 94305, USA.
Arkin
A P
AP
Ross
J
J
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D047108:Embryonic Development; D016200:Maturation-Promoting Factor / Q000378:metabolism*; D008954:Models, Biological; D012617:Sea Urchins; D014981:Xenopus
D016200:Maturation-Promoting Factor; D002118:Calcium