Human-specific SRGAP2 gene slows microglia maturation, study finds

August 31, 2026 at 05:00 AM2 min

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Columbia researchers found that human-specific copies of the SRGAP2 gene are nearly 10 times more abundant in microglia than in neurons. The gene dramatically slows microglia maturation, with human microglia taking four to eight years to mature versus three weeks in mice. The slow development may help microglia influence the human brain in ways that enable powerful cognitive abilities.

Key Facts

Human-specific copies of SRGAP2 are nearly 10 times more abundant in microglia than in neurons.
Human microglia take about four to eight years to mature, while mouse microglia reach maturity in roughly three weeks.
Microglia account for 5 to 10 percent of brain cells and help organize the developing brain by influencing synapse retention and elimination.
The study was led by Carlos Diaz-Salazar, PhD, in the lab of Franck Polleux, PhD, at Columbia's Zuckerman Institute.

SRGAP2 Gene Activity

The Polleux lab has studied SRGAP2 for more than 15 years, focusing on genes duplicated specifically in humans. Earlier work by Dr. Polleux showed that human-specific copies of SRGAP2 increase the number of synapses made by neurons while causing those synapses to mature very slowly. In the new research, Dr. Diaz-Salazar found that human-specific copies of SRGAP2 were nearly 10 times more abundant in microglia than in neurons. Dr. Polleux recalled asking, 'Why on Earth is this gene so active in microglia?'

Microglia Development Role

Over the past two decades, scientists have learned that microglia do much more than fight infections and help repair brain damage. These cells, which account for 5 to 10 percent of brain cells, help organize the developing brain. During development, microglia influence which synapses neurons retain and which ones are eliminated, and they can make synapses more or less responsive. Experiments using mice and human cells showed that the human-specific copies of SRGAP2 dramatically slow the development of human microglia. Human microglia take about four to eight years to mature, while microglia in mice reach maturity in roughly three weeks.

Human Brain Maturation

Compared with the brains of other mammals, the human brain develops over an unusually long period. Dr. Diaz-Salazar said the gene helps control the developmental tempo of neurons and has also been selected to control the development of microglia, keeping them in sync during development. Dr. Diaz-Salazar is now a researcher at the Hospital del Mar Medical Research Institute in Barcelona.