Shaping the Neocortex: Radial Glia and Astrocytes in Development and Evolution

The evolutionary expansion of the mammalian neocortex-especially in primates-underpins the emergence of advanced cognitive abilities. This process involved not only increased cortical surface area and neuronal output but also enhanced structural adaptations, such as cortical folding and glial morphological complexity. In this review, we examine the central roles of radial glia (RG) and astrocytes in driving neocortical expansion and evolution. We highlight the emergence of primate- and human-specific genes, which contribute to enhanced RG proliferation and neurogenesis in these species. We further explore how epigenetic regulation and dynamic chromatin architecture modulate RG behavior across species. At the cellular level, we discuss how morphological features-particularly the basal processes and specialized protrusions of RG-facilitate access to diverse extrinsic signals, promoting proliferative capacity and cortical complexity. We then turn to cortical folding, focusing on the role of astrocytes, and the functional relevance of folds in supporting brain homeostasis. Finally, we address astrocyte diversity, development, and evolutionary adaptation, with special emphasis on sex differences and primate-specific features. Comparative transcriptomic and morphological studies reveal that human astrocytes exhibit unique molecular signatures, expanded metabolic capacity, and higher morphological complexity. Together, these insights underscore the multifaceted contributions of RG and astrocytes to the evolutionary elaboration of the neocortex. They further provide a framework for understanding how cellular innovations shaped the modern primate brain in general, and human brain specifically.