Wnts Signal Transduction and Nervous System Development

Wnts are secreted proteins that play critical roles in mammalian brain development and function. During embryogenesis, Wnt genes not only control brain patterning and neuronal progenitor proliferation and differentiation, but also regulate axon pathfinding and synapse formation. Wnt genes also govern the proliferation of adult neural stem cells. Dr. Xi He’s laboratory in this IDDRC has made groundbreaking progress in charactering the mechanisms of Wnt signal transduction.  Among their discoveries are: (1) the demonstration that the  LDL receptor-related proteins, LRP5 and LRP6, are co-receptors for the canonical Wnt/beta-catenin signaling pathway and (2) the finding that the mammalian head inducer Dkk1 is a ligand for LRP5 and LRP6, and that Dkk1 inhibits Wnt signaling via disrupting Wnt-induced Fz-LRP6 complex formation.  These and numerous other findings of the He laboratory have had a major impact on our understanding of the mechanisms of Wnt signaling and the role of these important molecules in nervous system development.