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-prornoting 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.