Department of Biological Chemistry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Dev Neurobiol. 2022 Jul;82(5):408-427. doi: 10.1002/dneu.22879. Epub 2022 May 29.
Compared with that of even the closest primates, the human cortex displays a high degree of specialization and expansion that largely emerges developmentally. Although decades of research in the mouse and other model systems has revealed core tenets of cortical development that are well preserved across mammalian species, small deviations in transcription factor expression, novel cell types in primates and/or humans, and unique cortical architecture distinguish the human cortex. Importantly, many of the genes and signaling pathways thought to drive human-specific cortical expansion also leave the brain vulnerable to disease, as the misregulation of these factors is highly correlated with neurodevelopmental and neuropsychiatric disorders. However, creating a comprehensive understanding of human-specific cognition and disease remains challenging. Here, we review key stages of cortical development and highlight known or possible differences between model systems and the developing human brain. By identifying the developmental trajectories that may facilitate uniquely human traits, we highlight open questions in need of approaches to examine these processes in a human context and reveal translatable insights into human developmental disorders.
与最接近的灵长类动物相比，人类大脑皮层表现出高度专业化和扩展，这在很大程度上是在发育过程中出现的。尽管几十年来在小鼠和其他模型系统中的研究揭示了皮质发育的核心原则，这些原则在哺乳动物物种中得到了很好的保存，但转录因子表达、灵长类动物和/或人类中新的细胞类型以及独特的皮质结构方面的微小偏差将人类大脑皮层区分开来。重要的是，许多被认为驱动人类大脑皮层扩张的基因和信号通路也使大脑容易受到疾病的影响，因为这些因素的失调与神经发育和神经精神疾病高度相关。然而，要全面了解人类特有的认知和疾病仍然具有挑战性。在这里，我们回顾了皮质发育的关键阶段，并强调了模型系统和发育中的人类大脑之间已知或可能存在的差异。通过确定可能促进人类特有特征的发育轨迹，我们突出了需要在人类背景下研究这些过程的开放性问题，并揭示了可转化的人类发育障碍的见解。
