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The Power of Simplicity: Sea Urchin Embryos as in Vivo Developmental Models for Studying Complex Cell-to-cell Signaling Network Interactions
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Signaling cascades transmit information downstream and upstream but unlikely simultaneously.

Simona Catozzi1, Juan Pablo Di-Bella2, Alejandra C Ventura2

  • 1Université Côte d'Azur, CNRS, INLN, 1361 route des lucioles, Valbonne, 06560, France.

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|August 27, 2016
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Summary

Biochemical parameters control signal direction in cellular cascades. This study identifies conditions favoring forward or retro-signaling, revealing when retroactivity can be neglected and when cascades act as retro-signaling devices.

Keywords:
Drug designKinase inhibitorsMAPK cascadesRetroactivitySignaling cascades

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Area of Science:

  • Cellular biology
  • Biochemistry
  • Systems biology

Background:

  • Signal transduction enables cells to communicate with their environment.
  • Signaling cascades transmit biochemical information intracellularly.
  • Retroactivity allows perturbations to propagate upstream in cascades.

Purpose of the Study:

  • To compare conditions favoring forward versus retro-signaling in cellular cascades.
  • To elucidate the role of biochemical parameters in directing signal propagation.
  • To identify specific parameter sets that enhance forward or retro-signaling regimes.

Main Methods:

  • Mathematical analysis of cascade steady states using iterative maps.
  • Numerical and statistical approaches on a 3-tier signaling cascade model.
  • Random parameter scanning to compute the likelihood of signaling regimes.

Main Results:

  • Cascade steady states are governed by second-order iterative maps, coupling tiers three-by-three.
  • Biochemical parameters like kinetic rates and concentrations dictate signal direction.
  • Identified conditions that specifically enhance forward or retro-signaling.

Conclusions:

  • Parameter sets favoring forward and retro-signaling are generally opposed.
  • Retroactive effects are often negligible in efficient forward-signaling cascades.
  • Cascades can function as retro-signaling devices in specific, less-explored parameter spaces.