Synchrony dynamics during initiation, failure, and rescue of the segmentation clock.
The "segmentation clock" is thought to coordinate sequential segmentation of the body axis in vertebrate embryos. This clock comprises a multicellular genetic network of synchronized oscillators, coupled by intercellular Delta-Notch signaling. How this synchrony is established and how its loss determines the position of segmentation defects in Delta and Notch mutants are unknown. We analyzed the clock's synchrony dynamics by varying strength and timing of Notch coupling in zebra-fish embryos with techniques for quantitative perturbation of gene function. We developed a physical theory based on coupled phase oscillators explaining the observed onset and rescue of segmentation defects, the clock's robustness against developmental noise, and a critical point beyond which synchrony decays. We conclude that synchrony among these genetic oscillators can be established by simultaneous initiation and self-organization and that the segmentation defect position is determined by the difference between coupling strength and noise.
Riedel-Kruse
Ingmar H
IH
Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Pfotenhauerstrasse 108, 01307 Dresden, Germany. ingmar@caltech.edu
Müller
Claudia
C
Oates
Andrew C
AC
D000818:Animals; D001683:Biological Clocks / Q000235:genetics* / Q000502:physiology; D019521:Body Patterning / Q000235:genetics; D004151:Dipeptides / Q000494:pharmacology; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008433:Mathematics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020871:RNA Stability; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019170:Somites / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D004151:Dipeptides; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C492933:N-(N-(3,5-difluorophenylacetyl)alanyl)phenylglycine 4-benzoylbenzyl amide; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; D051881:Receptor, Notch1; D029961:Zebrafish Proteins; C064045:delta protein; C437805:notch1a protein, zebrafish