Brain developmental and cortical connectivity changes in transgenic monkeys carrying the human-specific duplicated gene SRGAP2C
作者机构：State Key Laboratory of Genetic Resources and EvolutionKunming Institute of ZoologyChinese Academy of Sciences National Resource Center for Non-Human PrimatesKunming Primate Research Centerand National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility)Kunming Institute of ZoologyChinese Academy of Sciences Kunming College of Life ScienceUniversity of Chinese Academy of Sciences Center for Excellence in Brain Science and Intelligence TechnologyInstitute of NeuroscienceCAS Key Laboratory of Primate NeurobiologyChinese Academy of Sciences Center for Excellence in Animal Evolution and GeneticsChinese Academy of Sciences
出 版 物：《National Science Review》 (国家科学评论(英文版))
年 卷 期：2023年第10卷第11期
页 面：45-60页
核心收录：
学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学]
基 金：supported by National Natural Science Foundation of China (U2002207, 32000406 and 32170628) Yunnan Province Science and Technology Department (2020-182) Youth Innovation Promotion Association of Chinese Academy of Sciences (to X.L.)
主 题：SRGAP2C transgenic monkey brain evolution brain development neurogenesis neoteny
摘 要：Human-specific duplicated genes contributed to phenotypic innovations during the origin of our own species, such as an enlarged brain and highly developed cognitive abilities. While prior studies on transgenic mice carrying the human-specific SRGAP2C gene have shown enhanced brain connectivity, the relevance to humans remains unclear due to the significant evolutionary gap between humans and rodents. In this study,to investigate the phenotypic outcome and underlying genetic mechanism of SRGAP2C, we generated transgenic cynomolgus macaques(Macaca fascicularis) carrying the human-specific SRGAP2C gene.Longitudinal MRI imaging revealed delayed brain development with region-specific volume changes,accompanied by altered myelination levels in the temporal and occipital regions. On a cellular level, the transgenic monkeys exhibited increased deep-layer neurons during fetal neurogenesis and delayed synaptic maturation in adolescence. Moreover, transcriptome analysis detected neotenic expression in molecular pathways related to neuron ensheathment, synaptic connections, extracellular matrix and energy metabolism. Cognitively, the transgenic monkeys demonstrated improved motor planning and execution skills. Together, our findings provide new insights into the mechanisms by which the newly evolved gene shapes the unique development and circuitry of the human brain.
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