Expansion of outer cortical CUX2 neurons requires adaptations for DNA repair - PubMed
3 hours ago
- #DNA repair
- #ATF4
- #cortical development
- ATF4 acts as a critical regulator of the DNA damage response, directly activating double-stranded DNA repair components like CIRBP, UBA52, and EBF1.
- Pan-cortical knockout of ATF4 (Emx1-Cre;Atf4fl/fl) reveals it is specifically required for the development of upper layer 2/3 neurons expressing CUX2.
- ATF4 functions to repair DNA damage and reduce cell death in embryonic radial glial progenitors, dependent on p53.
- CIRBP, a transcriptional target of ATF4, is necessary for normal phosphorylation of the DNA repair factor ATM.
- These findings highlight extraordinary DNA repair needs due to replicative stress during the development of CUX2+ neurons in the mammalian brain.