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Tissue mechanics modulate morphogen signalling to induce the head organiser.

Matyas Bubna-Litic1, Guillaume Charras2, Roberto Mayor3

  • 1Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.

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|December 4, 2024
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Mechanical stimulation during gastrulation enhances head organizer formation by modulating Activin-dependent mesoderm induction via β-catenin signaling. This finding has implications for understanding vertebrate development and synthetic organoid systems.

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Area of Science:

  • Developmental Biology
  • Cellular Mechanics
  • Molecular Signaling

Background:

  • Gastrulation establishes the vertebrate body plan through morphogenetic movements and germ layer specification.
  • The interplay between mechanical cues and biochemical signals in fate specification during gastrulation is not well understood.
  • Activin/Nodal/Smad2 signaling pathways are crucial for mesoderm induction and axial patterning.

Purpose of the Study:

  • To investigate the interplay between mechanical stimulation and Activin signaling in mesoderm induction and fate specification.
  • To understand how mechanical cues influence the formation of the head organizer.
  • To explore the role of β-catenin signaling in mediating the effects of mechanical stimulation.

Main Methods:

  • Utilized an ex vivo system of Activin-induced explants from Xenopus laevis animal cap ectoderm.
  • Applied uniaxial compression to explants during the induction period.
  • Analyzed gene expression of mesodermal and head organizer markers.
  • Assessed nuclear β-catenin activity and its modulation by mechanical stimulation.

Main Results:

  • Mechanical stimulation of Activin-induced explants increased the expression of dorsal mesoderm markers (chordin, goosecoid) and head mesoderm markers (cerberus 1).
  • Compression led to a loss of tissue elongation and an increase in nuclear β-catenin activity.
  • Activation of β-catenin signaling was sufficient to induce head organizer gene expression, and its inhibition rescued compression effects on a Wnt-signaling gene (siamois).

Conclusions:

  • Mechanical stimulation modulates Activin-dependent mesoderm induction, favoring head organizer formation.
  • Mechanical cues influence axial specification through β-catenin-dependent pathways.
  • Mechanics-dependent organizer induction may be conserved across vertebrate species and applicable to synthetic organoid development.