Cortical folding: when, where, how, and why?

Area of Science:

• Neurobiology
• Developmental Neuroscience
• Comparative Anatomy

Background:

• The folding of the cerebral cortex (gyrification) varies across mammalian species.
• Previous hypotheses for cortical folding include mechanical stress, axon guidance, localized cell proliferation, and external physical constraints.

Purpose of the Study:

• To synthesize existing theories and propose a unifying framework for mammalian cerebral cortex folding.
• To introduce and highlight the role of radial intercalation as a primary mechanism driving cortical expansion and folding.

Main Methods:

• Review and synthesis of existing theoretical and experimental research on cortical development.
• Introduction of a novel mechanism: radial intercalation of neurons at the apical surface of the cortical plate.

Main Results:

• A unifying framework integrating various proposed folding mechanisms is presented.
• Radial intercalation is identified as a key proximate force for tangential expansion, initiating cortical folding.
• The interplay of radial intercalation with proliferation rates and connectivity patterns explains both random and stereotyped fold formation.

Conclusions:

• Radial intercalation of neurons is a critical, previously underappreciated mechanism in cerebral cortex development.
• This mechanism, combined with other factors, provides a comprehensive explanation for the diversity of cortical folding patterns in mammals.