RT Journal Article
SR Electronic
T1 Hominin-specific NOTCH2 paralogs expand human cortical neurogenesis through regulation of Delta/Notch interactions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 221358
DO 10.1101/221358
A1 Suzuki, Ikuo K.
A1 Gacquer, David
A1 Van Heurck, Roxane
A1 Kumar, Devesh
A1 Wojno, Marta
A1 Bilheu, Angéline
A1 Herpoel, Adèle
A1 Chéron, Julian
A1 Polleux, Franck
A1 Detours, Vincent
A1 Vanderhaeghen, Pierre
YR 2017
UL http://biorxiv.org/content/early/2017/11/17/221358.1.abstract
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.