Long-range morphogen gradient formation by cell-to-cell signal propagation

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Johanna E.M. Dickmann - , Max-Planck-Institute for the Physics of Complex Systems (Author)
  • Jochen C. Rink - , Max Planck Institute for Multidisciplinary Sciences (Author)
  • Frank Jülicher - , Max-Planck-Institute for the Physics of Complex Systems, TUD Dresden University of Technology, Clusters of Excellence PoL: Physics of Life (Author)

Abstract

Morphogen gradients are a central concept in developmental biology. Their formation often involves the secretion of morphogens from a local source, that spread by diffusion in the cell field, where molecules eventually get degraded. This implies limits to both the time and length scales over which morphogen gradients can form which are set by diffusion coefficients and degradation rates. Towards the goal of identifying plausible mechanisms capable of extending the gradient range, we here use theory to explore properties of a cell-to-cell signaling relay. Inspired by the millimeter-scale wnt-expression and signaling gradients in flatworms, we consider morphogen-mediated morphogen production in the cell field. We show that such a relay can generate stable morphogen and signaling gradients that are oriented by a local, morphogen-independent source of morphogen at a boundary. This gradient formation can be related to an effective diffusion and an effective degradation that result from morphogen production due to signaling relay. If the secretion of morphogen produced in response to the relay is polarized, it further gives rise to an effective drift. We find that signaling relay can generate long-range gradients in relevant times without relying on extreme choices of diffusion coefficients or degradation rates, thus exceeding the limits set by physiological diffusion coefficients and degradation rates. A signaling relay is hence an attractive principle to conceptualize long-range gradient formation by slowly diffusing morphogens that are relevant for patterning in adult contexts such as regeneration and tissue turn-over.

Details

Original languageEnglish
Article number066001
JournalPhysical biology
Volume19
Issue number6
Publication statusPublished - 7 Sept 2022
Peer-reviewedYes

External IDs

PubMed 35921820

Keywords

Keywords

  • cellular signaling, development, long-range patterning, morphogen gradients, planarians, tissue patterning, Wnt signaling