Mutations of WD40-repeat protein 62 (WDR62) were identified to be associated with human autosomal recessive primary microcephaly (MCPH).However, the underlying mechanism is unclear.Here, we generate Wdr62 deficient mice which exhibit reduced brain size.We find that knockdown in rat embryonic cortex and deficiency in mice of WDR62 disturb neurogenesis by promoting premature differentiation of neural progenitor cells (NPCs), which can be rescued by wild-type human WDR62 but not by the MCPH-associated WDR62 mutants.We demonstrate that WDR62 controls neurogenesis through the regulation of JNK signaling by interaction with MEKK3.