title: Changes in oscillatory dynamics in the cell cycle of early Xenopus laevis embryos.
abstract: During the early development of Xenopus laevis embryos, the first mitotic cell cycle is long (∼85 min) and the subsequent 11 cycles are short (∼30 min) and clock-like. Here we address the question of how the Cdk1 cell cycle oscillator changes between these two modes of operation. We found that the change can be attributed to an alteration in the balance between Wee1/Myt1 and Cdc25. The change in balance converts a circuit that acts like a positive-plus-negative feedback oscillator, with spikes of Cdk1 activation, to one that acts like a negative-feedback-only oscillator, with a shorter period and smoothly varying Cdk1 activity. Shortening the first cycle, by treating embryos with the Wee1A/Myt1 inhibitor PD0166285, resulted in a dramatic reduction in embryo viability, and restoring the length of the first cycle in inhibitor-treated embryos with low doses of cycloheximide partially rescued viability. Computations with an experimentally parameterized mathematical model show that modest changes in the Wee1/Cdc25 ratio can account for the observed qualitative changes in the cell cycle. The high ratio in the first cycle allows the period to be long and tunable, and decreasing the ratio in the subsequent cycles allows the oscillator to run at a maximal speed. Thus, the embryo rewires its feedback regulation to meet two different developmental requirements during early development.
authors: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, United States of America ; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America ; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Tony Y-C
authors: TY
authors: Tsai
authors: Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America ; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Julie A
authors: JA
authors: Theriot
authors: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, United States of America ; Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.
authors: James E
authors: JE
authors: Ferrell
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000201:enzymology; D025461:Feedback, Physiological; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D014982:Xenopus laevis / Q000196:embryology*; D020666:ras-GRF1 / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C489725:Myt1 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins; D020666:ras-GRF1; C530005:WEE1 protein, Xenopus; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase