Nuclear Factor of Activated T Cells (NFAT) Proteins Repress Canonical Wnt Signaling via Its Interaction with Dishevelled (Dvl) Protein and Participate in Regulating Neural Progenitor Cell Proliferation and Differentiation

The Ca2+ signaling pathway appears to regulate the processes of the early development through its antagonism of canonical Wnt/beta-catenin signaling pathway. However, the underlying mechanism is still poorly understood. Here, we show that nuclear factor of activated T cells (NFAT), a component of Ca2+ signaling, interacts directly with Dishevelled (Dvl) in a Ca2+-dependent manner. A dominant negative form of NFAT rescued the inhibition of the Wnt/beta-catenin pathway triggered by the Ca2+ signal. NFAT functioned downstream of beta-catenin without interfering with its stability, but influencing the interaction of beta-catenin with Dvl by its competitively binding to Dvl. Furthermore, we demonstrate that NFAT is a regulator in the proliferation and differentiation of neural progenitor cells by modulating canonical Wnt/beta-catenin signaling pathway in the neural tube of chick embryo. Our findings suggest that NFAT negatively regulates canonical Wnt/beta-catenin signaling by binding to Dvl, thereby participating in vertebrate neurogenesis.