Intrinsic neural stem cell properties define brain hypersensitivity to genotoxic stress.

ABSTRACT: Impaired replication has been previously linked to growth retardation and microcephaly; however, why the brain is critically affected compared with other organs remains elusive. Here, we report the differential response between early neural progenitors (neuroepithelial cells [NECs]) and fate-committed neural progenitors (NPs) to replication licensing defects. Our results show that, while NPs can tolerate altered expression of licensing factors, NECs undergo excessive replication stress, identified by impaired replication, increased DNA damage, and defective cell-cycle progression, leading eventually to NEC attrition and microcephaly. NECs that possess a short G1 phase license and activate more origins than NPs, by acquiring higher levels of DNA-bound MCMs. In vivo G1 shortening in NPs indu

SUBMITTER: Kalogeropoulou A 

PROVIDER: S-EPMC9214316 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature