GSE124339
Efficient induction of Gcm1 under folate deficiency promotes vertebrate neural development by Wnt/ß-catenin pathway activation
Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/ß-catenin pathway leads to defective anteroposterior patterning, resulting in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We report here that in C57BL/6C mouse embryonic stem cells (mESC), folate deficiency activates Wnt/ß-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promotes the formation of the Gcm1/ß-catenin/T-cell factor (TCF4) complex to regulate the Wnt target gene transactivation through the Wnt-responsive elements. Moreover, the enhanced transcriptional activity of Gcm1 is found to be dependent on CREB binding protein. Lastly, in NTDs mouse models and low folate NTDs human brain samples, Gcm1 and Wnt/ß-catenin target genes related to neural tube closure are specifically overexpressed. These results indicate that low folate promotes Wnt/ß-catenin signaling via activating Gcm1, leading to aberrant vertebrate neural development Overall design: Examination of 1 transcription factor in 1 cell type with different treatment