Wnt signal activation induces midbrain specification through direct binding of the beta-catenin/TCF4 complex to the EN1 promoter in human pluripotent stem cells

Abstract

Brain development: Specifying differentiation into midbrain cells An evolutionarily conserved signaling pathway triggers the differentiation of human pluripotent stem cells (hPSCs) into functional midbrain neurons. Dong-Wook Kim at Yonsei University, South Korea, and colleagues explored the mechanisms through which the Wnt signal regulates neuronal cell fate. They found that both Wnt and fibroblast growth factor signaling are required to increase the expression of EN1, a midbrain-specific gene, in a neural precursor cell population derived from hPSCs. They showed that activation of the Wnt signaling pathway leads to the formation of a protein complex containing beta-catenin that directly interacts with the promoter region of this gene to initiate transcription. Insights into how stem cells differentiate into midbrain-specific cell types will aid our understanding of neurological disorders affecting this brain region, such as Parkinson’s disease, and may lead to identification of novel therapeutic targets.