This study examined whether human-specific SRGAP2B/C gene paralogs drive neotenic (prolonged/delayed) maturation of cortical microglia in humans, and whether this microglial neoteny in turn shapes the timing of synaptic development, using hiPSC-derived microglia xenotransplantation and mouse genetic models.
SRGAP2B/C — the only human-specific gene duplications expressed in human microglia — were both necessary and sufficient to induce neotenic structural microglial maturation, and this delayed microglial maturation measurably altered the timing of synaptic development in vivo.
The study relies on xenotransplantation of hiPSC-derived microglia into mouse hosts, which may not fully recapitulate the human brain environment. The full text content of individual pages was not extractable, limiting assessment of specific sample sizes, statistical detail, and secondary outcomes.
While not directly clinical, these findings identify SRGAP2B/C as a human-specific genetic mechanism linking microglial developmental timing to circuit formation — a potential framework for understanding neurodevelopmental disorders tied to accelerated or disrupted synaptic maturation.
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