Biophysical basis for brain folding and misfolding patterns in ferrets and humans

Area of Science:

• Neurodevelopmental Biology
• Computational Neuroscience
• Comparative Neuroanatomy

Background:

• Understanding neurodevelopment necessitates bridging molecular genetics with macroscopic brain structures and neurological function.
• Cortical gyrification, the folding of the cerebral cortex, is crucial for higher cognitive functions.
• Ferret models offer valuable insights into cortical morphogenesis due to their brain structure.

Purpose of the Study:

• To elucidate the multiscale processes connecting genetic factors to brain development and function.
• To investigate the mechanical principles governing brain gyrification using computational and physical models.
• To identify key drivers of cortical dysmorphogenesis and their relevance to human brain malformations.

Main Methods:

• Magnetic resonance imaging (MRI) of ferret brains.
• In vitro physical gel modeling of brain tissue.
• In silico numerical simulations of brain gyrification.
• Analysis of genetically manipulated animal models.

Main Results:

• Cerebral cortical thickness and expansion rate identified as primary drivers of abnormal brain development (dysmorphogenesis).
• In silico models successfully simulated normal gyrification and allowed examination of developmental aberrations.
• Analogous cortical malformations in ferrets and humans were explained, linked to specific genetic defects.

Conclusions:

• Genetic causes and mechanical factors (brain geometry, differential growth) interact to drive brain morphogenesis.
• Computational and experimental models provide a unified perspective on brain development across species.
• This research deepens the mechanistic understanding of neurodevelopment and cortical malformations.