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Mechanisms for positional signalling by morphogen transport: a theoretical study

M Kerszberg1, L Wolpert

  • 1Neurobiologie Moléculaire, Institut pasteur, 25 rue du Docteur Roux, Paris Cedex 15, F-75724, France. mkersz@pasteur.fr

Journal of Theoretical Biology
|June 6, 1998
PubMed
Summary

Morphogen diffusion alone, even with receptor binding, fails to create concentration gradients. Instead, a novel receptor-aided transport model explains morphogen propagation along cell membranes during embryonic development.

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Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Biophysics

Background:

  • Cellular activity gradients are crucial for embryonic development.
  • Morphogen distribution is thought to establish these gradients, but propagation mechanisms remain unclear.
  • Simple molecular diffusion is a proposed, yet debated, mechanism for morphogen spread.

Purpose of the Study:

  • To investigate the role of morphogen-receptor binding in establishing positional signaling.
  • To explore alternative mechanisms for morphogen propagation beyond simple diffusion.
  • To model a novel receptor-aided transport system for morphogens like TGF-beta family members.

Main Methods:

  • Analysis of morphogen-receptor binding kinetics.
  • Development of a computational model for receptor-aided directed diffusion.

Related Experiment Videos

  • Simulation of morphogen propagation along cell membranes and transfer between cells.

    • Main Results:

    • Morphogen-receptor binding alone prevents concentration-based positional signaling, leading to a saturated distribution.
    • A diffusion-based model suggests cells can infer position by integrating signals over time.
    • The proposed receptor-aided diffusion model demonstrates efficient morphogen propagation along membranes and cell-to-cell transfer.
    • This model predicts dependence on cell-cell proximity and does not require protein synthesis or degradation.

    Conclusions:

    • Simple diffusion with receptor binding is insufficient for concentration-based morphogen gradients.
    • Temporal integration of signals offers a potential, albeit indirect, positional readout.
    • Receptor-aided directed diffusion presents a viable mechanism for directed morphogen transport and signaling in development.
    • This mechanism highlights the importance of cell-cell interactions in morphogen distribution.