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Brain Developmental and Cortical Connectivity Changes in Transgenic Monkeys Carrying the Human-specific Duplicated Gene SRGAP2
论文题目: Brain Developmental and Cortical Connectivity Changes in Transgenic Monkeys Carrying the Human-specific Duplicated Gene SRGAP2
作者: Xiaoyu Meng , Qiang Lin, Xuerui Zeng , Jin Jiang, Min L, Xin Luo, Kaimin Chen, Haixu Wu, Yan Hu, Cirong Liu, Bing Su
联系作者: sub@mail.kiz.ac.cn
发表年度: 2023
DOI: DOI: 10.1093/nsr/nwad281
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

刊物名称: National Science Review
论文出处: https://academic.oup.com/nsr/article/10/11/nwad281/7342471?login=true
影响因子: 20.7(2022IF)
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