Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development

• 来源期刊: 国家科学评论（英文版）
• 年，卷（期）: 2019,（3）
• 页码范围: 480-493
• 页数: 14页
• 语种: 英文
• DOI: 10.1093/nsr/nwz043

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.