Microglia play important roles in supporting neuronal function and shaping the connectivity in the brain. There is evidence for microglial changes in neurodevelopmental diseases like autism spectrum disorder (ASD), but the role of ASD-linked genes in microglia has not been systematically investigated.
A project led by Olivia Teter in the Kampmann lab used CRISPRi-based functional genomics to systematically assess the impact of ASD risk gene knockdown on microglia activation and phagocytosis. This screen identified ADNP, a high-confidence ASD risk genes, as a modifier of microglial synaptic pruning. We found that microglia with ADNP loss have altered endocytic trafficking, remodeled proteomes, and increased motility in coculture.
The article describing these results was published in Molecular Psychiatry:
Teter OM, McQuade A, Hagan V, Liang W, Dräger NM, Sattler SM, Holmes BB, Castillo VC, Papakis V, Leng K, Boggess S, Nowakowski TJ, Wells J, Kampmann M (2025)
CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning.
Molecular Psychiatry. doi: 10.1038/s41380-025-02997-z. Epub ahead of print.