Zhao Jinyue, Feng Chao, Wang Wenwen, Su Libo, Jiao Jianwei
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Beijing Institute for Stem Cell and Regenerative Medicine, Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Cell Discov. 2022 Nov 22;8(1):124. doi: 10.1038/s41421-022-00469-0.
Neocortex expansion and folding are related to human intelligence and cognition, but the molecular and cellular mechanisms underlying cortical folding remain poorly understood. Here, we report that the human gene SERPINA3 is linked to gyrification. Specifically, the overexpression of SERPINA3 induced neocortical folding, increased the abundance of neurons, and improved cognitive abilities. Further, SERPINA3 promoted proliferation of the outer radial glia (oRG, also referred to as the basal radial glia) and increased the number of upper-layer neurons. The downstream target Glo1 was determined to be involved in SERPINA3-induced gyrification. Moreover, SERPINA3 increased the proliferation of oRG by binding to the Glo1 promoter. Assessment of behavior performance showed enhanced cognitive abilities in SERPINA3 knock-in mice. Our findings will enrich the understanding of neocortical expansion and gyrification and provide insights into possible treatments for intellectual disability and lissencephaly syndrome.
新皮质的扩张和折叠与人类智力和认知相关，但皮质折叠背后的分子和细胞机制仍知之甚少。在此，我们报告人类基因SERPINA3与脑回形成有关。具体而言，SERPINA3的过表达诱导了新皮质折叠，增加了神经元数量，并改善了认知能力。此外，SERPINA3促进了外侧放射状胶质细胞（oRG，也称为基底放射状胶质细胞）的增殖，并增加了上层神经元的数量。确定下游靶点Glo1参与了SERPINA3诱导的脑回形成。此外，SERPINA3通过与Glo1启动子结合增加了oRG的增殖。行为表现评估显示，SERPINA3基因敲入小鼠的认知能力增强。我们的研究结果将丰富对新皮质扩张和脑回形成的理解，并为智力障碍和无脑回综合征的可能治疗提供见解。
