Download PDF Subjects Neural progenitors Neuronal development Abstract During mammalian evolution, excitatory neurons in upper cortical layer 2 and layer 3 (L2/3) have shown a disproportionate expansion compared with other layers 1 , 2 , 3 , 4。
Replicative expansion of cortical neural progenitors is associated with considerable oxidative DNA damage。
Here we show that activating transcription factor 4 (ATF4) has roles as a critical regulator of the DNA damage response, directly activating components of double-stranded DNA repair, including CIRBP, UBA52 and EBF1。
Notably, pan-cortical knockout ( Emx1-Cre; Atf4 fl/fl ) demonstrates that ATF4 is required specifically for the development of upper layer 2/3 neurons, marked by the expression of cut-like homeobox 2 protein, CUX2。
ATF4 functions to repair DNA damage and attenuate cell death of embryonic radial glial progenitors in a p53-dependent manner。
They further indicate that there are extraordinary requirements for DNA repair after replicative stress in CUX2 + neurons during mammalian brain development。
来源：Nature
