Folding brains: from development to disease modeling.

Area of Science:

• Neuroscience
• Developmental Biology
• Evolutionary Biology

Background:

• The human brain's cerebral cortex exhibits large size and intricate folding, essential for higher cognitive functions.
• Cortex folding is a conserved trait across mammals, arising from complex developmental processes.
• Dysregulation of these processes can lead to pathological malformations of human cortex folding.

Purpose of the Study:

• To review current knowledge on molecular, cellular, histogenic, and mechanical mechanisms of cerebral cortex folding.
• To examine the evolutionary changes in cortex folding across mammalian evolution.
• To discuss pathological malformations, their developmental origins, and genetic underpinnings.

Main Methods:

• Review of existing literature on brain development and evolution.
• Synthesis of data on cellular and molecular mechanisms driving cortical folding.
• Analysis of genetic causes and animal/in vitro models for studying cortex malformations.

Main Results:

• Cortical folding results from integrated processes involving neural stem cells, progenitor lineages, neuronal migration, differentiation, and genetic regulation.
• Mechanical stress and strain on developing neural tissue are key drivers of orderly cortical deformation.
• Investigating genetic causes of malformations has significantly advanced understanding of key developmental events.

Conclusions:

• Understanding the interplay of molecular, cellular, and mechanical factors is crucial for comprehending brain folding.
• Studying evolutionary trajectories and developmental disorders provides insights into conserved and divergent mechanisms.
• Further research using animal and in vitro models is needed to address remaining challenges in understanding brain folding.