The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis.

ABSTRACT: Mutations in components of the exon junction complex (EJC) are associated with neurodevelopment and disease. In particular, reduced levels of the RNA helicase EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS) and copy number variations are linked to intellectual disability. Consistent with this, Eif4a3 haploinsufficient mice are microcephalic. Altogether, this implicates EIF4A3 in cortical development; however, the underlying mechanisms are poorly understood. Here, we use mouse and human models to demonstrate that EIF4A3 promotes cortical development by controlling progenitor mitosis, cell fate and survival. Eif4a3 haploinsufficiency in mice causes extensive cell death and impairs neurogenesis. Using Eif4a3;p53 compound mice, we show that apoptosis has the most impact on early neurogenes

SUBMITTER: Lupan BM 

PROVIDER: S-EPMC10233715 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature