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Related Experiment Video

Updated: Dec 31, 2025

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Coupling delay controls synchronized oscillation in the segmentation clock.

Kumiko Yoshioka-Kobayashi1,2, Marina Matsumiya1,3, Yusuke Niino4

  • 1Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.

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|January 10, 2020
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Summary
This summary is machine-generated.

The lunatic fringe (Lfng) gene is crucial for synchronizing Hes7 gene oscillations in mouse embryos. Lfng regulates cell-cell communication via Notch signaling, ensuring proper somite segmentation and preventing developmental defects.

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Area of Science:

  • Developmental Biology
  • Cellular Oscillations
  • Gene Regulation

Background:

  • Cellular activities are coordinated at the population level through cell-cell coupling.
  • The somite segmentation clock relies on synchronized Hes7 gene oscillations in the presomitic mesoderm (PSM).
  • Notch signaling is essential for synchronizing these oscillations, with its inhibition leading to somite fusion.

Purpose of the Study:

  • To elucidate the mechanism by which Notch signaling regulates the synchronicity of Hes7 oscillations.
  • To investigate the role of the Notch modulator lunatic fringe (Lfng) in PSM cell synchronization.

Main Methods:

  • Development of a live-imaging system using a novel fluorescent reporter (Achilles) fused to Hes7.
  • Single-cell resolution monitoring of Hes7 oscillations in mouse PSM.
  • Comparative analysis of wild-type and Lfng-null PSM cells, including dissociated and mixed cultures.
  • Optogenetic Notch signaling reporter assays and mathematical modeling.

Main Results:

  • Wild-type cells exhibit rapid correction of Hes7 oscillation phase fluctuations.
  • Lfng-null PSM cells show desynchronized and dampened Hes7 oscillations, indicating Lfng's role in cell-cell coupling.
  • Lfng delays intercellular Notch signaling transmission, and its absence shortens this coupling delay.
  • A compound lengthening the coupling delay partially rescues Hes7 oscillation amplitude and synchrony in Lfng-null PSM.

Conclusions:

  • Lunatic fringe (Lfng) is essential for maintaining synchronized Hes7 oscillations in the PSM by controlling intercellular coupling delay.
  • The study reveals a delay control mechanism in oscillatory networks crucial for somite segmentation.
  • Proper intercellular coupling delay is vital for synchronized oscillations in developmental processes.