Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany; Neuroscience Center, HiLIFE - Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland.
Université de Paris, NeuroDiderot, Inserm, 75019 Paris, France.
Neuron. 2021 Feb 3;109(3):408-419. doi: 10.1016/j.neuron.2020.11.014. Epub 2020 Dec 10.
The neocortex, the seat of our higher cognitive abilities, has expanded in size during the evolution of certain mammals such as primates, including humans. This expansion occurs during development and is linked to the proliferative capacity of neural stem and progenitor cells (NPCs) in the neocortex. A number of cell-intrinsic and cell-extrinsic factors have been implicated in increasing NPC proliferative capacity. However, NPC metabolism has only recently emerged as major regulator of NPC proliferation. In this Perspective, we summarize recent insights into the role of NPC metabolism in neocortical development and neurodevelopmental disorders and its relevance for neocortex evolution. We discuss certain human-specific genes and microcephaly-implicated genes that operate in, or at, the mitochondria of NPCs and stimulate their proliferation by promoting glutaminolysis. We also discuss other metabolic pathways and develop a perspective on how metabolism mechanistically regulates NPC proliferation in neocortical development and how this contributed to neocortex evolution.
新皮层是我们更高认知能力的所在地，在某些哺乳动物（包括人类）的进化过程中，其大小已经扩大。这种扩张发生在发育过程中，与新皮层中神经干细胞和祖细胞（NPC）的增殖能力有关。许多内在和外在的细胞因素都被认为可以增加 NPC 的增殖能力。然而，NPC 代谢最近才成为 NPC 增殖的主要调节因子。在本观点中，我们总结了 NPC 代谢在新皮层发育和神经发育障碍中的作用及其与新皮层进化的相关性的最新见解。我们讨论了某些人类特异性基因和小头畸形相关基因，这些基因在 NPC 的线粒体中起作用或位于其中，并通过促进谷氨酰胺分解来刺激其增殖。我们还讨论了其他代谢途径，并探讨了代谢如何通过调节 NPC 增殖来影响新皮层发育的机制，以及这种机制如何促进新皮层进化。
