Orchestrated neuronal migration and cortical folding: A computational and experimental study.

Area of Science:

• Neuroscience
• Biophysics
• Developmental Biology

Background:

• Brain development involves complex genetic, biochemical, and mechanical processes.
• Cortical folding increases brain surface area through neuronal proliferation and migration.
• Existing models often lack mechanistic detail for spatio-temporal neuronal development.

Purpose of the Study:

• To provide mechanistic insights into brain development and cortical folding.
• To develop a biomechanical model coupling cell division, migration, and volumetric growth.
• To track neuronal cohorts born at different developmental stages.

Main Methods:

• Developed a biomechanical model simulating cell division, migration, and volumetric growth.
• Modeled neuronal cohorts using an advection-diffusion process, with cell density driving volume changes.
• Numerically implemented the model using Abaqus/Standard with user-defined element subroutines.
• Calibrated the model using in utero electroporation data from ferret brains to track neuronal cohorts.

Main Results:

• Simulations of cortical folding qualitatively matched experimental observations in ferrets.
• The model successfully tracked spatio-temporal development of distinct neuronal cohorts.
• Provided a mechanistic understanding of how cell dynamics influence cortical surface expansion.

Conclusions:

• The biomechanical model offers a robust platform for studying brain development and cortical folding.
• The findings contribute to understanding neurodevelopmental processes and malformations.
• Open-access data and model implementation facilitate future research in neurological disorders.