Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo

Area of Science:

• Developmental Biology
• Cellular Mechanics
• Tissue Engineering

Background:

• Collective cell migration is crucial for development and disease, involving molecular and mechanical cues.
• The influence of tissue mechanics on in vivo collective cell migration remains largely unexplored.
• Xenopus laevis neural crest cells serve as a model for collective cell migration, similar to cancer invasion.

Purpose of the Study:

• To investigate the role of mechanical cues in the collective migration of Xenopus laevis neural crest cells.
• To elucidate the mechanisms by which tissue mechanics influence embryonic morphogenesis.
• To establish a link between gastrulation, tissue mechanics, and neural crest cell migration.

Main Methods:

• Mechanical and molecular manipulations of Xenopus laevis embryos.
• Analysis of neural crest cell migration and epithelial-to-mesenchymal transition.
• Investigation of mechanosensation pathways involving integrin-vinculin-talin.

Main Results:

• Head mesoderm stiffening precedes and triggers cephalic neural crest cell collective migration.
• Neural crest cells employ integrin-vinculin-talin mediated mechanosensation to detect mesoderm stiffness.
• Convergent extension during gastrulation increases mesoderm stiffness, thereby coordinating neural crest migration.

Conclusions:

• Mesoderm stiffening is both necessary and sufficient to initiate neural crest collective migration.
• Tissue mechanics, specifically substrate stiffness, can trigger collective cell migration and epithelial-to-mesenchymal transition in vivo.
• Convergent extension acts as a mechanical coordinator of morphogenesis, linking gastrulation to neural crest migration through altered tissue mechanics.