File:Nwz043.pdf

English: 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 to the observed brain developmental delay of the transgenic monkeys. More importantly, the transgenic monkeys exhibited better short-term memory and shorter reaction time compared to the wild type controls in the delayed matching to sample task. The presented data represents the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model, and it values the use of nonhuman primates in understanding human unique traits.