Glutaminolysis and the Control of Neural Progenitors in Neocortical Development and Evolution

Multiple types of neural progenitor cells (NPCs) contribute to the development of the neocortex, a brain region responsible for our higher cognitive abilities. Proliferative capacity of NPCs varies among NPC types, developmental stages, and species. The higher proliferative capacity of NPCs in the developing human neocortex is thought to be a major contributing factor why humans have the most expanded neocortex within primates. Recent studies have shed light on the importance of cell metabolism in the neocortical NPC proliferative capacity. Specifically, glutaminolysis, a metabolic pathway that converts glutamine to glutamate and then to α-ketoglutarate, has been shown to play a critical role in human NPCs, both in apical and basal progenitors. In this review, we summarize our current knowledge of NPC metabolism, focusing especially on glutaminolysis, and discuss the role of NPC metabolism in neocortical development, evolution, and neurodevelopmental disorders, providing a broader perspective on a newly emerging research field.