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

TL;DR

Reducing Neurod2 in Xenopus tadpoles stops brain cells from maturing and causes seizures, suggesting a role in neural development.

Contribution

This study reveals that Neurod2 deficiency retains progenitor cells in a proliferative state, linking it to hyper-excitability and seizures.

Findings

Neurod2 knockdown increases cell cycle gene expression in tadpole brains.

Neurod2 deficiency decreases nerve growth factor and chromatin modifying gene expression.

Loss of Neurod2 prevents neural progenitor cells from differentiating and exiting the cell cycle.

Abstract

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.

Figures