机构:[1]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.[2]Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.[3]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.[4]Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translation Medicine, Kunming University of Science and Technology, Kunming, 650500, China.[5]Cerebral Microcirculation Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA[6]Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599-7160, USA[7]Department of Computer Science, University of North Carolina, Chapel Hill, NC 27599- 7160, USA.[8]Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China[9]Department of Medical Imaging, the First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China昆明医科大学附属第一医院[10]Department of Minimally Invasive Neurosurgery, the First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China昆明医科大学附属第一医院[11]Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China.
Brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive. Here, we successfully generated 11 transgenic rhesus monkeys (8 first-generation and 3 second-generation) carrying human copies of MCPH1, an important gene for brain development and brain evolution. Brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation, resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys, similar to the known evolutionary change of developmental delay (neoteny) in humans. Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes, providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys. More importantly, the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task. The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits.
基金:
Strategic Priority Research Program of the Chinese Academy of SciencesChinese Academy of Sciences [XDB13000000]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31730088, 31621062]; Youth Innovation Promotion Association of CAS
第一作者机构:[1]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.[2]Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.[3]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.
共同第一作者:
通讯作者:
通讯机构:[1]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.[2]Primate Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.[3]Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.
推荐引用方式(GB/T 7714):
Shi Lei,Luo Xin,Jiang Jin,et al.Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development[J].NATIONAL SCIENCE REVIEW.2019,6(3):480-493.doi:10.1093/nsr/nwz043.
APA:
Shi, Lei,Luo, Xin,Jiang, Jin,Chen, Yongchang,Liu, Cirong...&Su, Bing.(2019).Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development.NATIONAL SCIENCE REVIEW,6,(3)
MLA:
Shi, Lei,et al."Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development".NATIONAL SCIENCE REVIEW 6..3(2019):480-493