Axons pull on the brain, but tension does not drive cortical folding

Area of Science:

• Neuroscience
• Developmental Biology
• Biophysics

Background:

• Cerebral cortex folding is vital for brain development and function.
• Abnormal cortical folding is associated with neurological disorders like schizophrenia and autism.
• The biomechanical forces driving cortical folding remain poorly understood.

Purpose of the Study:

• To investigate the mechanisms responsible for cerebral cortex folding.
• To test the hypotheses that folding is driven by differential cortical growth or axonal tension.
• To elucidate the biomechanics of cortical morphogenesis.

Main Methods:

• Microdissection assays were performed on developing ferret brains to measure tissue tension.
• Computational modeling, specifically finite element analysis, was employed to simulate folding.
• Experimental and computational approaches were combined to evaluate competing hypotheses.

Main Results:

• Axons in the developing ferret brain exhibit tension, but it is not directed in a way that would cause folding.
• Differential growth of the cortex, coupled with subplate remodeling, generates outward folds.
• Computational models support differential growth as the primary driver of cortical folding.
• Local variations in growth initiation can explain consistent folding patterns.

Conclusions:

• Differential cortical growth, not axonal tension, is the primary mechanism driving cerebral cortex folding.
• Understanding these biomechanical processes is crucial for comprehending normal brain development and associated disorders.
• This study demonstrates the power of integrating experimental and computational methods in developmental biology.