摘要：SummaryProper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein that interacts with transcription factors and chromatin remodeling complexes, is required for the embryonic formation of the cerebral cortex. Here we show that Akirin2 plays a mechanistically distinct role in maintaining healthy neurons during cortical maturation. Restricting Akirin2 loss to excitatory cortical neurons resulted in progressive neurodegeneration via necroptosis and severe cortical atrophy with age. Comparing transcriptomes from Akirin2-null postnatal neurons and cortical progenitors revealed that targets of the tumor suppressor p53, a regulator of both proliferation and cell death encoded byTrp53, were consistently upregulated. Reduction ofTrp53rescued neurodegeneration in Akirin2-null neurons. These data: (1) implicate Akirin2 as a critical neuronal maintenance protein, (2) identify p53 pathways as mediators of Akirin2 functions, and (3) suggest Akirin2 dysfunction may be relevant to neurodegenerative diseases.Graphical abstractDisplay OmittedHighlights•Akirin2 is a nuclear protein involved in proliferation but maintained in postmitotic neurons•Postnatal Akirin2 knockout in cortical neurons leads to slow neurodegeneration•RNASeq identifies the dysregulation of p53-related genes in knockout neurons•Akirin2-null neurons die by necroptosis that depends on p53 upregulationBiological sciences; Molecular biology; Neuroscience; Cell biology
