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Cell. 2018 May 31;173(6):1370-1384.e16. doi: 10.1016/j.cell.2018.03.067. Epub 2018 May 31.

Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation.

Author information

1
Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM) and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KULeuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KUL, 3000 Leuven, Belgium.
2
Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM), 1070 Brussels, Belgium.
3
Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM) and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium.
4
Department of Neuroscience, Columbia University Medical Center, Columbia University, New York, NY 10027, USA.
5
Université Libre de Bruxelles (ULB), Institute for Interdisciplinary Research (IRIBHM) and ULB Neuroscience Institute (UNI), 1070 Brussels, Belgium; VIB-KULeuven Center for Brain & Disease Research, 3000 Leuven, Belgium; Department of Neurosciences, Leuven Brain Institute, KUL, 3000 Leuven, Belgium; WELBIO, ULB, B-1070 Brussels, Belgium. Electronic address: pierre.vanderhaeghen@kuleuven.vib.be.

Abstract

The cerebral cortex underwent rapid expansion and increased complexity during recent hominid evolution. Gene duplications constitute a major evolutionary force, but their impact on human brain development remains unclear. Using tailored RNA sequencing (RNA-seq), we profiled the spatial and temporal expression of hominid-specific duplicated (HS) genes in the human fetal cortex and identified a repertoire of 35 HS genes displaying robust and dynamic patterns during cortical neurogenesis. Among them NOTCH2NL, human-specific paralogs of the NOTCH2 receptor, stood out for their ability to promote cortical progenitor maintenance. NOTCH2NL promote the clonal expansion of human cortical progenitors, ultimately leading to higher neuronal output. At the molecular level, NOTCH2NL function by activating the Notch pathway through inhibition of cis Delta/Notch interactions. Our study uncovers a large repertoire of recently evolved genes active during human corticogenesis and reveals how human-specific NOTCH paralogs may have contributed to the expansion of the human cortex.

KEYWORDS:

Notch; brain development; cerebral cortex; human evolution; neurogenesis

PMID:
29856955
PMCID:
PMC6092419
DOI:
10.1016/j.cell.2018.03.067
[Indexed for MEDLINE]
Free PMC Article

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