Neurod2 knockdown in Xenopus laevis tadpole brain retains cells in a proliferating, progenitor-like state

Neurogenic differentiation factor 2, encoded by the NEUROD2 gene, is a proneural transcription factor required for neuronal differentiation and survival. Haploinsufficiency of NEUROD2 can cause neurodevelopmental disorders with or without seizures in human infants and causes spontaneous seizures in Xenopus tadpoles. We compared transcriptomes of whole brains dissected from F ₀ neurod2 ^-/- (mosaic) stage NF47 Xenopus laevis tadpoles to those of control siblings. neurod2 knockdown increased expression of cell cycle-associated genes and decreased nerve growth factor (NGF) and chromatin modifying genes. Our results suggest Neurod2 deficiency prevents neural progenitor cells exiting the cell cycle and differentiating, predisposing the brain to hyper-excitability.