Single-cell-resolution imaging of the impact of Notch signaling and mitosis on segmentation clock dynamics

Dev Cell. 2012 Nov 13;23(5):995-1005. doi: 10.1016/j.devcel.2012.09.009.

Abstract

Vertebrate body segmentation is controlled by the segmentation clock, a molecular oscillator involving transcriptional oscillations of cyclic genes in presomitic mesoderm cells. The rapid and highly dynamic nature of this oscillating system has proved challenging for study at the single-cell level. We achieved visualization of clock activity with a cellular level of resolution in living embryos, allowing direct comparison of oscillations in neighbor cells. We provide direct evidence that presomitic mesoderm cells oscillate asynchronously in zebrafish Notch pathway mutants. By tracking oscillations in mitotic cells, we reveal that a robust cell-autonomous, Notch-independent mechanism resumes oscillations after mitosis. Finally, we find that cells preferentially divide at a certain oscillation phase, likely reducing the noise generated by cell division in cell synchrony and suggesting an intriguing relationship between the mitotic cycle and clock oscillation.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biological Clocks
  • Body Patterning
  • Gene Expression Regulation, Developmental
  • Genes, Reporter
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • Mitosis
  • Mutation
  • Plasmids / genetics
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • Zebrafish / embryology*
  • Zebrafish / genetics
  • Zebrafish / metabolism*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Receptors, Notch
  • Zebrafish Proteins
  • her1 protein, zebrafish