Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development
Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development作者机构：State Key Laboratory of Genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Primate Research Center Kunming Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences Yunnan Key Laboratory of Primate Biomedical Research Institute of Primate Translation Medicine Kunming University of Science and Technology Department of Psychiatry University of North CarolinaChapel Hill Department of Computer Science University of North CarolinaChapel Hill Key Laboratory of Animal Models and Human Disease Mechanisms Kunming Institute of Zoology Chinese Academy of Sciences Department of Medical Imaging the First Affiliated Hospital of Kunming Medical University Department of Minimally Invasive Neurosurgery the First Affiliated Hospital of Kunming Medical University
出 版 物：《National Science Review》 (国家科学评论(英文版))
年 卷 期：2019年第6卷第3期
页 面：480-493页
核心收录：
学科分类：0710[理学-生物学] 07[理学] 071008[理学-发育生物学]
基 金：supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB13000000to B.S.) the National Natural Science Foundation of China(31730088 and 31621062 to B.S.) the Youth Innovation Promotion Association of CAS(to L.S.)
主 题：human evolution brain development MCPH1 transgenic monkey neoteny cognition
摘 要：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.
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