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It has been reported that all-trans retinoic acid(ATRA)exposure at early mouse neurulation could induce neural tube defects(NTDs),but the mechanisms were not clear yet.In our study,we found high dose of ATRA could lead to NTDs by inducing apoptosis of neural stem cells(NSCs),caspases and CaMKII-TAK1-p38 signaling were involved in this process.