Extension of cortical synaptic development distinguishes humans from chimpanzees and macaques

Xiling Liu, Mehmet Somel, Lin Tang, Zheng Yan, Xi Jiang, Song Guo, Yuan Yuan, Liu He, Anna Oleksiak, Yan Zhang, Na Li, Yuhui Hu, Wei Chen, Zilong Qiu, Svante Pääbo, Philipp Khaitovich

Research output: Contribution to journalArticlepeer-review

153 Citations (Scopus)


Over the course of ontogenesis, the human brain and human cognitive abilities develop in parallel, resulting in a phenotype strikingly distinct from that of other primates. Here, we used microarrays and RNA-sequencing to examine human-specific gene expression changes taking place during postnatal brain development in the prefrontal cortex and cerebellum of humans, chimpanzees, and rhesus macaques. We show that the most prominent human-specific expression change affects genes associated with synaptic functions and represents an extreme shift in the timing of synaptic development in the prefrontal cortex, but not the cerebellum. Consequently, peak expression of synaptic genes in the prefrontal cortex is shifted from <1 yr in chimpanzees and macaques to 5 yr in humans. This result was supported by protein expression profiles of synaptic density markers and by direct observation of synaptic density by electron microscopy. Mechanistically, the human-specific change in timing of synaptic development involves the MEF2A-mediated activity-dependent regulatory pathway. Evolutionarily, this change may have taken place after the split of the human and the Neanderthal lineages.

Original languageEnglish
Pages (from-to)611-622
Number of pages12
JournalGenome Research
Issue number4
Publication statusPublished - Apr 2012
Externally publishedYes


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