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Updated: Aug 8, 2025

An Optogenetic Method to Control and Analyze Gene Expression Patterns in Cell-to-cell Interactions
Published on: March 22, 2018
Controlling periodic long-range signalling to drive a morphogenetic transition
Hugh Z Ford1, Angelika Manhart2,3, Jonathan R Chubb1
1Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Cells use cyclic adenosine monophosphate (cAMP) waves for long-range signaling during collective migration. Increased wave frequency, driven by a positive feedback loop, triggers cell movement and regulates developmental patterns.
Area of Science:
- Cellular biology
- Developmental biology
- Biophysics
Background:
- Cells communicate using signal relay for tissue-scale information transmission.
- The mechanisms generating information in signal relay systems are not fully understood.
- Periodic cyclic adenosine monophosphate (cAMP) waves in Dictyostelium discoideum facilitate collective cell migration.
Purpose of the Study:
- To investigate how coding features of signal relay are generated.
- To determine the mechanisms regulating cAMP wave circulation and frequency.
- To elucidate the positive feedback loop between cell state and signaling patterns.
Main Methods:
- Live imaging of Dictyostelium cell signaling.
- Optogenetic perturbation of cell signaling states.
- Mathematical modeling and general theory of excitable media.
- Mechanical perturbations to test competing models.
Main Results:
- Cell migration is initiated by an increased wave frequency from the signaling center.
- Wave frequency is modulated by cAMP wave circulation, organizing long-range signals.
- A positive feedback model, where wave circulation enhances signal relay and circulation rate, best explains the observed signaling dynamics.
- Models based on cell density or spatial patterning do not account for temporal signaling evolution.
Conclusions:
- A positive feedback mechanism between cell state and signaling patterns regulates long-range signal coding.
- This feedback loop is crucial for driving collective cell migration and morphogenesis.
- Understanding cAMP wave dynamics provides insights into cellular communication and pattern formation.
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