WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression.

Olig2 transcription factor is essential for the maintenance of neural progenitor cells (NPCs) in the pMN domain and their sequential specification into motor neurons (MNs) and oligodendrocyte precursor cells (OPCs). The expression of Olig2 rapidly declines in newly generated MNs. However, Olig2 expression persists in later-born OPCs and antagonizes the expression of MN-related genes. The mechanism underlying the differential expression of Olig2 in MNs and oligodendrocytes remains unknown. Here, we report that activation of WNT/β-catenin signaling in pMN lineage cells abolished Olig2 expression coupled with a dramatic increase of Ngn2 expression. Luciferase reporter assay showed that Ngn2 inhibited Olig2 promoter activity. Overexpression of Ngn2-EnR transcription repressor blocked the expression of Olig2 in ovo. Our results suggest that down-regulation of WNT-Ngn2 signaling contributes to oligodendrogenesis from the pMN domain and the persistent Olig2 expression in OPCs.