ArticleNeuron2024
Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition.
Article in Neuron, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Human-specific morphoregulatory signatures in basal radial glia characterise neocortex evolution.Nature communications · 2026Article
- A Human Accelerated Region Drives Opposing Heterochronic Changes in Craniofacial and Limb Development.bioRxiv : the preprint server for biology · 2026Article
- Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development.Neuron · 2026Article
- Article
- A human-specific genetic modifier reconfigures large-scale cortical network dynamics underlying behavioral performance.bioRxiv : the preprint server for biology · 2026Article
- Genomic approaches for understanding the evolution of the human brain.Nature neuroscience · 2026Review
- A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex.Science (New York, N.Y.) · 2026Article
- Spatiotemporal histogenesis of the developing human cerebellum reveals dynamic layering of Bergmann glia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Intrinsic elaboration of prefrontal modularity: a dual-control model of axon bundling and synaptic docking.Frontiers in neuroanatomy · 2026Review
- Reduced Adult Neurogenesis in Humans Results From a Tradeoff Rather Than Direct Negative Selection.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Chimeric brain models: Unlocking insights into human neural development, aging, diseases, and cell therapies.Neuron · 2025Review
- Mapping the developmental profile of ventricular zone-derived neurons in the human cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Exploring the singularity of human neurons: keep calm and carry on.Frontiers in synaptic neuroscience · 2025Review
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Authors and funding
17 authors.
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Abstract
Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic gene SRGAP2A, in human cortical pyramidal neurons (CPNs) xenotransplanted in the mouse cortex. Downregulation of SRGAP2B/C in human CPNs led to strongly accelerated synaptic development, indicating their requirement for the neoteny that distinguishes human synaptogenesis. SRGAP2B/C genes promoted neoteny by reducing the synaptic levels of SRGAP2A,thereby increasing the postsynaptic accumulation of the SYNGAP1 protein, encoded by a major intellectual disability/autism spectrum disorder (ID/ASD) gene. Combinatorial loss-of-function experiments in vivo revealed that the tempo of synaptogenesis is set by the reciprocal antagonism between SRGAP2A and SYNGAP1, which in human CPNs is tipped toward neoteny by SRGAP2B/C. Thus, HS genes can modify the phenotypic expression of genetic mutations leading to ID/ASD through the regulation of human synaptic neoteny.
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