ArticleScientific reports2019
The human-specific paralogs SRGAP2B and SRGAP2C differentially modulate SRGAP2A-dependent synaptic development.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development.Neuron · 2026Article
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- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- A human-specific genetic modifier reconfigures large-scale cortical network dynamics underlying behavioral performance.bioRxiv : the preprint server for biology · 2026Article
- Genetic diversity and regulatory features of human-specific NOTCH2NL duplications.Cell genomics · 2026Article
- A female-specific role for Slit1 in prenatal stress-induced depression vulnerability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Purkinje cell intrinsic activity shapes cerebellar development and function.Nature communications · 2026Article
- Descriptive transcriptomic profiling differentiates oral leukoplakia from proliferative verrucous leukoplakia and reveals distinct molecular signatures.Medicina oral, patologia oral y cirugia bucal · 2026Article
- Segmentally duplicated regulatory elements undergo human-specific rewiring.bioRxiv : the preprint server for biology · 2025Article
- A deep learning pipeline for accurate and automated restoration, segmentation, and quantification of dendritic spines.Cell reports methods · 2025Article
- Lineage-associated Human Divergently-paired Genes Exhibit Structural and Regulatory Characteristics.Genomics, proteomics & bioinformatics · 2025Article
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- Human CLOCK enhances neocortical function.Nature neuroscience · 2025Article
- Human-specific gene expansions contribute to brain evolution.bioRxiv : the preprint server for biology · 2025Article
- Complete sequencing of ape genomes.Nature · 2025Article
- Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition.Neuron · 2024Article
- Complete sequencing of ape genomes.bioRxiv : the preprint server for biology · 2024Article
- Human-specific genetic modifiers of cortical architecture and function.Current opinion in genetics & development · 2024Review
- Zebrafish models of human-duplicatedbioRxiv : the preprint server for biology · 2024Article
- Loss of the polarity protein Par3 promotes dendritic spine neoteny and enhances learning and memory.iScience · 2024Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Human-specific gene duplications (HSGDs) have recently emerged as key modifiers of brain development and evolution. However, the molecular mechanisms underlying the function of HSGDs remain often poorly understood. In humans, a truncated duplication of SRGAP2A led to the emergence of two human-specific paralogs: SRGAP2B and SRGAP2C. The ancestral copy SRGAP2A limits synaptic density and promotes maturation of both excitatory (E) and inhibitory (I) synapses received by cortical pyramidal neurons (PNs). SRGAP2C binds to and inhibits all known functions of SRGAP2A leading to an increase in E and I synapse density and protracted synapse maturation, traits characterizing human cortical neurons. Here, we demonstrate how the evolutionary changes that led to the emergence of SRGAP2 HSGDs generated proteins that, in neurons, are intrinsically unstable and, upon hetero-dimerization with SRGAP2A, reduce SRGAP2A levels in a proteasome-dependent manner. Moreover, we show that, despite only a few non-synonymous mutations specifically targeting arginine residues, SRGAP2C is unique compared to SRGAP2B in its ability to induce long-lasting changes in synaptic density throughout adulthood. These mutations led to the ability of SRGAP2C to inhibit SRGAP2A function and thereby contribute to the emergence of human-specific features of synaptic development during evolution.
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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.