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Updated: Jun 27, 2025

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Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness.

Parnian Doostdar1, Joshua Hawley1, Kunal Chopra1

  • 1Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health,The University of Manchester, Oxford Road, Manchester M13 9PT, UK.

Development (Cambridge, England)
|April 29, 2024
PubMed
Summary

Altering the bHLH transcription factor Her6 dynamics in zebrafish telencephalon progenitors revealed increased oscillations and heterogeneity. Cell coupling mechanisms compensate for altered gene expression, maintaining phenotypic robustness despite single-cell dynamic changes.

Keywords:
Her6NeurogenesisOscillationsTelencephalonZebrafish

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Area of Science:

  • Developmental biology
  • Neuroscience
  • Genetics

Background:

  • The bHLH transcription factor Her6 plays a role in neural development.
  • Understanding gene expression dynamics at the single-cell level is crucial for developmental processes.

Purpose of the Study:

  • To investigate the impact of altering Her6 protein expression dynamics on embryonic zebrafish telencephalon development.
  • To explore the relationship between single-cell gene expression heterogeneity and tissue-level robustness.

Main Methods:

  • Utilized a Her6:Venus reporter in homozygous zebrafish embryos.
  • Employed 4D single-cell tracking to monitor Her6 dynamics in neural telencephalic progenitors.
  • Experimentally disrupted Notch signaling and used computational modeling to analyze Her6 protein stability effects.

Main Results:

  • Her6 exhibits oscillatory expression in neural telencephalic progenitors.
  • Fusion with a protein destabilization (PEST) domain altered Her6 dynamics, increasing oscillations and heterogeneity.
  • Tissue-level changes emerged from cell coupling, with transient alterations in telencephalon size and later minor increases in differentiation markers.

Conclusions:

  • Cell coupling acts as a compensatory mechanism, conferring phenotypic robustness despite abnormal single-cell gene expression dynamics.
  • Her6 expression dynamics significantly influence neural progenitor behavior and tissue development.
  • This study highlights the emergent properties of cellular interactions in maintaining developmental homeostasis.