Identification of Human Specific Expressed Genes in the Fetal Brain

The expansion of human neocortex is the cornerstone of highly developed cognitive abilities which distinguishes human from primates, but the molecular basis underlying it remains elusive. Here, we comprehensively compared the transcriptomes of neural precursor cells-enriched germinal zone (GZ) and neurons-enriched cortical plate (CP) of neocortex among human, macaque and mouse to identify human specific expressed genes (HSEGs) for each layer. The data identified that the HSEGs have evolved to transfer between the layers and also annotated the primate originated HSEGs. Further, we assessed the contributions of regulatory factors to the evolution of HSEGs. Finally, we analyzed such a new identified HSEG named CCNB1IP1 and discovered that the evolution of cis regulatory elements caused the gene to develop human specific pattern. Subsequent functional results showed that CCNB1IP1 could repress the expression of cell cycle related genes by interacting with E2F1, thereby shortening the length of the G1 phase. Thus, our study is firstly to identify HSEGs in the fetal cortex and reveals how CCNB1IP1 regulated cell cycle progress which contributed to the expansion of human cortex potentially.