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Excitable Dynamics and Yap-Dependent Mechanical Cues Drive the Segmentation Clock.

Alexis Hubaud1, Ido Regev2, L Mahadevan3

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS (UMR 7104), Inserm U964, Université de Strasbourg, Illkirch 67400, France; Department of Genetics, Harvard Medical School and Department of Pathology, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA.

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Summary

Vertebrate segmentation relies on the segmentation clock. This study shows oscillations are a collective cell property, triggered by quorum sensing and mechanical cues, revealing the clock as an excitable system.

Keywords:
NotchYapclockexcitabilityexcitable systemoscillationspresomitic mesodermsegmentationsomitogenesis

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Area of Science:

  • Developmental biology
  • Cellular dynamics
  • Genetics

Background:

  • Vertebrate body axis segmentation into somites and vertebrae depends on the segmentation clock.
  • The segmentation clock involves rhythmic signaling pathway activity in the presomitic mesoderm (PSM).
  • It remains unclear if these oscillations are intrinsic to single cells or a population phenomenon.

Purpose of the Study:

  • To investigate whether segmentation clock oscillations are a single-cell or population-level property.
  • To establish in vitro culture conditions for observing stable cellular oscillations.
  • To explore the role of quorum sensing and mechanical cues in triggering these oscillations.

Main Methods:

  • Developed in vitro culture conditions to achieve stable cellular oscillations.
  • Utilized Yap and Notch signaling pathways to trigger oscillations.
  • Manipulated Yap-dependent mechanical cues to alter cellular states.

Main Results:

  • Demonstrated that segmentation clock oscillations are a collective property of PSM cells.
  • Showed that oscillations can be actively triggered in vitro via a dynamical quorum sensing signal.
  • Confirmed that manipulating Yap-dependent mechanical cues can switch isolated PSM cells from quiescent to oscillatory states.

Conclusions:

  • The segmentation clock functions as an excitable system.
  • Oscillations are a collective cell behavior, not solely an intrinsic single-cell property.
  • Introduces a new paradigm for studying vertebrate morphogenesis dynamics.