PT  - JOURNAL ARTICLE
AU  - Suzuki, Ikuo K.
AU  - Gacquer, David
AU  - Van Heurck, Roxane
AU  - Kumar, Devesh
AU  - Wojno, Marta
AU  - Bilheu, Angéline
AU  - Herpoel, Adèle
AU  - Chéron, Julian
AU  - Polleux, Franck
AU  - Detours, Vincent
AU  - Vanderhaeghen, Pierre
TI  - Hominin-specific NOTCH2 paralogs expand human cortical neurogenesis through regulation of Delta/Notch interactions
AID  - 10.1101/221358
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 221358
4099  - http://biorxiv.org/content/early/2017/11/17/221358.1.short
4100  - http://biorxiv.org/content/early/2017/11/17/221358.1.full
AB  - The human cerebral cortex has undergone rapid expansion and increased complexity during recent evolution. Hominid-specific gene duplications represent a major driving force of evolution, but their impact on human brain evolution remains unclear. Using tailored RNA sequencing (RNAseq), we profiled the spatial and temporal expression of Hominid-specific duplicated (HS) genes in the human fetal cortex, leading to the identification of a repertoire of 36 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Among these we focused on NOTCH2NL, previously uncharacterized HS paralogs of NOTCH2. NOTCH2NL promote the clonal expansion of human cortical progenitors by increasing self-renewal, ultimately leading to higher neuronal output. NOTCH2NL function by activating the Notch pathway, through inhibition of Delta/Notch interactions. Our study uncovers a large repertoire of recently evolved genes linking genomic evolution to human brain development, and reveals how hominin-specific NOTCH paralogs may have contributed to the expansion of the human cortex.