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

Authors: Suzuki, Ikuo K.; Gacquer, David; Van Heurck, Roxane; Kumar, Devesh; Wojno, Marta; Bilheu, Angeline; Herpoel, Adele; +5 Authors

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

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.

Country
Belgium
Keywords

Biochemistry & Molecular Biology, Notch, SEGMENTAL DUPLICATIONS, Neurogenesis, brain development, Article, human evolution, Neural Stem Cells, CEREBRAL-CORTEX, Cluster Analysis, Humans, Amino Acid Sequence, Receptor, Notch2, 11 Medical and Health Sciences, In Situ Hybridization, COPY NUMBER VARIATION, Cerebral Cortex, Neurons, Science & Technology, 31 Biological sciences, Gene Expression Profiling, Calcium-Binding Proteins, Gene Expression Regulation, Developmental, Membrane Proteins, HUMAN BRAIN EVOLUTION, Cell Differentiation, Cell Biology, PYRAMIDAL NEURONS, 32 Biomedical and clinical sciences, Sciences bio-médicales et agricoles, 06 Biological Sciences, MOUSE NEOCORTEX, NERVOUS-SYSTEM, neurogenesis, PROGENITOR CELLS, Gene Expression Regulation, cerebral cortex, Intercellular Signaling Peptides and Proteins, Life Sciences & Biomedicine, PLURIPOTENT STEM-CELLS, RADIAL GLIA, Developmental Biology, Signal Transduction

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    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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    influence
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    Top 1%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 0.1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
333
Top 0.1%
Top 1%
Top 0.1%
Green
hybrid