Multiscale mechanisms of cell migration during development: theory and experiment

Area of Science:

• Developmental Biology
• Cell Biology
• Biophysics

Background:

• Long-distance cell migration is crucial for embryonic development, morphogenesis, and cancer progression.
• The precise mechanisms governing directed migration of cell subpopulations remain incompletely understood.

Purpose of the Study:

• To investigate and model the mechanisms driving long-distance neural crest (NC) cell migration.
• To differentiate the roles of leading versus trailing cell subpopulations in collective migration.

Main Methods:

• Utilized embryonic neural crest (NC) cell migration as a model system.
• Integrated experimental observations with theoretical modeling and simulations.
• Performed cell ablation and transplantation experiments to test mechanistic predictions.

Main Results:

• A simple chemotaxis model was insufficient to explain NC cell migration dynamics.
• Model simulations predicted and experiments confirmed that leading cells respond to long-range cues and trailing cells to short-range cues.
• Distinct gene expression and orientation patterns were observed between leading and trailing NC cell subpopulations, influenced by tissue growth.

Conclusions:

• Neural crest cell migration is regulated by a sophisticated interplay between leading and trailing cell subpopulations.
• Leading cells establish and respond to a cell-induced chemotactic gradient, guiding trailing cells via short-range interactions.
• This mechanistic model explains the maintenance of directed, multicellular streams during long-distance migration.