The article by Pasko Rakic explores the evolutionary expansion and elaboration of the cerebral neocortex, which is crucial for human mental abilities. The author discusses how genetic mutations and new molecular pathways have led to distinct evolutionary advancements in the neocortex. Key points include: 1. **Developmental Biology and Evo-Devo**: The neocortex's evolution is best understood through comparative studies of gene expression and developmental events in different mammalian species, using the Evo-Devo approach. 2. **Cortical Development Features**: The cerebral cortex is a unique cellular sheet composed of projection and interneurons, with neurons generated in transient proliferative zones and migrating to their final positions. The inside-out gradient of neurogenesis is a distinctive feature, where neurons bypass previous generations. 3. **Evolutionary Ascent of the Cortex**: The human cerebral cortex expanded primarily by increasing surface area without thickness, achieved through radial unit hypothesis, which involves symmetrical divisions of neural stem cells and linear increases within columns. 4. **Development of Convolutions**: The formation of convolutions in the human cortex is associated with the development of the intermediate zone, which contributes to the stereotyped shape and orientation of convolutions. 5. **Evolutionary Adaptation of Radial Glial Cells**: Radial glial cells, which serve as neural stem cells and guides for neuronal migration, have diversified to accommodate cortical expansion and convolution development. 6. **Multiplication and Elaboration of Cortical Maps**: The evolution of distinct cortical areas involves differential gene expression in neural stem cells, leading to species-specific parcellation. Morphogenetic factors like Fgf8 play a crucial role in regionalization. 7. **Introduction of New Cell Types and Migratory Pathways**: Human-specific features include the subpial granular layer, migration from the Ganglionic Eminence to the thalamus, and the presence of Predecessor cells, which are not observed in other species. 8. **Genetic Differences**: Despite small genetic differences between humans and other animals, these differences have significant functional implications, particularly in the expansion of association areas in the neocortex. 9. **Region-Specific Gene Expression**: Recent studies using advanced microarray techniques have identified significant transcriptional differences between neocortical areas, providing insights into the genetic mechanisms underlying human brain evolution. The article emphasizes the importance of understanding these evolutionary processes to unravel the secrets of human mental abilities and to inform the pathogenesis and therapies for human-specific neuropsychiatric disorders.The article by Pasko Rakic explores the evolutionary expansion and elaboration of the cerebral neocortex, which is crucial for human mental abilities. The author discusses how genetic mutations and new molecular pathways have led to distinct evolutionary advancements in the neocortex. Key points include: 1. **Developmental Biology and Evo-Devo**: The neocortex's evolution is best understood through comparative studies of gene expression and developmental events in different mammalian species, using the Evo-Devo approach. 2. **Cortical Development Features**: The cerebral cortex is a unique cellular sheet composed of projection and interneurons, with neurons generated in transient proliferative zones and migrating to their final positions. The inside-out gradient of neurogenesis is a distinctive feature, where neurons bypass previous generations. 3. **Evolutionary Ascent of the Cortex**: The human cerebral cortex expanded primarily by increasing surface area without thickness, achieved through radial unit hypothesis, which involves symmetrical divisions of neural stem cells and linear increases within columns. 4. **Development of Convolutions**: The formation of convolutions in the human cortex is associated with the development of the intermediate zone, which contributes to the stereotyped shape and orientation of convolutions. 5. **Evolutionary Adaptation of Radial Glial Cells**: Radial glial cells, which serve as neural stem cells and guides for neuronal migration, have diversified to accommodate cortical expansion and convolution development. 6. **Multiplication and Elaboration of Cortical Maps**: The evolution of distinct cortical areas involves differential gene expression in neural stem cells, leading to species-specific parcellation. Morphogenetic factors like Fgf8 play a crucial role in regionalization. 7. **Introduction of New Cell Types and Migratory Pathways**: Human-specific features include the subpial granular layer, migration from the Ganglionic Eminence to the thalamus, and the presence of Predecessor cells, which are not observed in other species. 8. **Genetic Differences**: Despite small genetic differences between humans and other animals, these differences have significant functional implications, particularly in the expansion of association areas in the neocortex. 9. **Region-Specific Gene Expression**: Recent studies using advanced microarray techniques have identified significant transcriptional differences between neocortical areas, providing insights into the genetic mechanisms underlying human brain evolution. The article emphasizes the importance of understanding these evolutionary processes to unravel the secrets of human mental abilities and to inform the pathogenesis and therapies for human-specific neuropsychiatric disorders.