Human-Only Gene May Help Explain Our Brainpower, Study Finds

Researchers at Columbia University's Zuckerman Institute have discovered that human microglia — the brain's most abundant immune cells — mature far more slowly than the same cells in other animals, much like human neurons already do. The findings, led by Carlos Diaz-Salazar and published in the journal Neuron, came from the lab of Franck Polleux.

For more than 15 years, Polleux's lab has studied SRGAP2, one of several dozen genes duplicated specifically in humans. Earlier work from the lab showed that human-specific copies of SRGAP2 increase the number of synapses — the connections neurons make with each other — while also causing those synapses to mature very slowly, producing a denser, stronger network of neural connections.

In the new study, Diaz-Salazar found that human-specific copies of SRGAP2 are nearly 10 times more abundant in microglia than in neurons, a discovery that surprised him. Microglia make up 5 to 10 percent of brain cells and do more than fight infection: they help shape the developing brain by influencing which synapses neurons keep or eliminate. Experiments in mice and human cells showed that the human-specific SRGAP2 copies dramatically slow microglia development — human microglia take about 4 to 8 years to mature, compared with roughly 3 weeks in mice.

Scientists call the human brain's unusually long developmental period neoteny, thought to play an important role in advanced human cognitive abilities. The findings suggest SRGAP2 may help coordinate this slow pace across both neurons and microglia so the two develop in sync, and researchers now want to determine exactly how the gene produces this effect. Because microglia have also been linked to neurodevelopmental disorders and neurodegenerative disease, Polleux said the findings bring researchers a step closer to understanding what makes human microglia special in the context of brain disease.