ArticleCell2018
Human-Specific NOTCH2NL Genes Affect Notch Signaling and Cortical Neurogenesis.
Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 317 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
317 citing papers in PubMed, 3 syntheses or guidelines pooled it, 552 citations in OpenAlex.
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- Advances of NOTCH2NLC Repeat Expansions and Associated Diseases: A Bibliometric and Meta-analysis.Molecular neurobiology · 2024Pooled it
- Clinical features of neuronal intranuclear inclusion disease with seizures: a systematic literature review.Frontiers in neurology · 2024Pooled it
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- Functional Mapping of Neurodevelopmental Disease Pathways to Key Neurodevelopmental Processes Represented in the Developmental Neurotoxicity In Vitro Testing Battery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spatial architecture of autism pathogenesis reveals mosaic structural disarray during early development.Nature communications · 2026Article
- Genetic diversity and regulatory features of human-specific NOTCH2NL duplications.Cell genomics · 2026Article
- Duplicate, diversify, repeat: The evolution of NOTCH2NL.Cell genomics · 2026Article
- miR-151-5p regulates neural stem cell fate by targeting APH1A to modulate Notch signaling gradients.Stem cell reports · 2026Article
257 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 8 institutions in 2 countries.
Funding
Abstract
Genetic changes causing brain size expansion in human evolution have remained elusive. Notch signaling is essential for radial glia stem cell proliferation and is a determinant of neuronal number in the mammalian cortex. We find that three paralogs of human-specific NOTCH2NL are highly expressed in radial glia. Functional analysis reveals that different alleles of NOTCH2NL have varying potencies to enhance Notch signaling by interacting directly with NOTCH receptors. Consistent with a role in Notch signaling, NOTCH2NL ectopic expression delays differentiation of neuronal progenitors, while deletion accelerates differentiation into cortical neurons. Furthermore, NOTCH2NL genes provide the breakpoints in 1q21.1 distal deletion/duplication syndrome, where duplications are associated with macrocephaly and autism and deletions with microcephaly and schizophrenia. Thus, the emergence of human-specific NOTCH2NL genes may have contributed to the rapid evolution of the larger human neocortex, accompanied by loss of genomic stability at the 1q21.1 locus and resulting recurrent neurodevelopmental disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.