Wnt7a regulates multiple steps of neurogenesis.

The signaling protein Wnt7a has been implicated in ensuring nerve cells called neurons reach their correct targets and in the formation of synapses between neurons; however studies of the role of Wnt7a in the early steps of neurogenesis have just begun. Using a mouse model, we found that Wnt7a is essential for perpetuating the self-renewal of neural stem cells in the brain and for converting and maturing these stem cells into neurons. Genetically engineered mice in which the Wnt7a gene had been deleted had substantially fewer neural stem cells than did mice that still expressed the Wnt7a gene. Further, loss of Wnt7a increased the rate of cell cycle exit in neural progenitor cells in the hippocampus, a region of the brain important for learning and memory. Loss of Wnt7a expression also led to a substantial decrease in the number of newborn neurons in this region, as well as impaired development and growth of these neurons. We also found that Wnt7a regulated neural stem cell proliferation and differentiation by activating cell signaling pathways controlled by a protein known as beta-catenin. Wnt7a exercises critical control over multiple steps of neurogenesis by regulating genes involved in both cell cycle control and neuronal differentiation. Further, this study suggests that modulation of Wnt7a expression could provide a means to improve learning and memory.