Research Programme Mutations in DONSON and other DNA replication genes cause primary microcephaly, a condition where the brain fails to grow to its normal size. While we assume that fewer cells produced during normal development account for this defect, the cell and molecular mechanism linking DNA replication defects to abnormal brain development remain to be established. We currently use Donson knock-in mice that recapitulate primary microcephaly seen in human individuals.In the short-term future, we will combine gene editing in human embryonic stem cells and iPSCs to establish 2D and 3D brain organoid models of DONSON deficiency to address the causes of neurodevelopmental defects upon replisome defects. This article was published on 2026-01-16
