ArticleNeuron2016
SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses.
Article in Neuron, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 129 citations in OpenAlex.
- Human-specific SRGAP2 paralogs synchronize neotenic microglial maturation and synaptic development.Neuron · 2026Article
- Clustered inputs engage dendritic nonlinearities and calcium signaling to support efficient place-field formation in CA1 pyramidal neurons.Cell reports · 2026Article
- A human-specific microRNA controls the timing of excitatory synaptogenesis.Nature communications · 2026Article
- Evolutionary causes and consequences of gene duplication.Nature reviews. Genetics · 2026Review
- A human-specific genetic modifier reconfigures large-scale cortical network dynamics underlying behavioral performance.bioRxiv : the preprint server for biology · 2026Article
- Charting the human-specific properties of gene expression networks in the infant prefrontal cortex.Science advances · 2026Article
- A female-specific role for Slit1 in prenatal stress-induced depression vulnerability.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Early life shifts in cortical inhibitory-excitatory balance underlies sensitive periods and skill development.Frontiers in cellular neuroscience · 2026Article
- A deep learning pipeline for accurate and automated restoration, segmentation, and quantification of dendritic spines.Cell reports methods · 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
- Toxicity and absorption of polystyrene micro-nanoplastics in healthy and Crohn's disease human duodenum-chip models.Journal of hazardous materials · 2025Article
- Human-specific genetic hallmarks in neocortical development: focus on neural progenitors.Current opinion in genetics & development · 2024Review
- Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition.Neuron · 2024Article
- Polyethyleneimine facilitates the growth and electrophysiological characterization of iPSC-derived motor neurons.Scientific reports · 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
9 more citing papers are in PubMed but not listed here.
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7 authors at 3 institutions in 2 countries.
Funding
Abstract
The proper function of neural circuits requires spatially and temporally balanced development of excitatory and inhibitory synapses. However, the molecular mechanisms coordinating excitatory and inhibitory synaptogenesis remain unknown. Here we demonstrate that SRGAP2A and its human-specific paralog SRGAP2C co-regulate the development of excitatory and inhibitory synapses in cortical pyramidal neurons in vivo. SRGAP2A promotes synaptic maturation, and ultimately the synaptic accumulation of AMPA and GABAA receptors, by interacting with key components of both excitatory and inhibitory postsynaptic scaffolds, Homer and Gephyrin. Furthermore, SRGAP2A limits the density of both types of synapses via its Rac1-GAP activity. SRGAP2C inhibits all identified functions of SRGAP2A, protracting the maturation and increasing the density of excitatory and inhibitory synapses. Our results uncover a molecular mechanism coordinating critical features of synaptic development and suggest that human-specific duplication of SRGAP2 might have contributed to the emergence of unique traits of human neurons while preserving the excitation/inhibition balance.
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