Signaling neurogenesis

MethoxyRoxy / WIKIMEDIA

The paper: D.C. Lie et al., "Wnt signaling regulates adult hippocampal neurogenesis," Nature, 437:1370-5, 2005. (Cited in 79 papers)

The finding: After discovering neurogenesis in humans in 1998, Fred Gage's group at the Salk Institute in California went looking for signals that control the phenomenon in rodents. They found that overexpressing the signaling molecule Wnt increased neurogenesis, while inhibiting Wnt abolished the growth of new neurons.

The other players: Wnt was the first major regulator identified in neurogenesis, says first author Dieter Chichung Lie, now at GSF-Research Center for Environment and Health in Germany. Since then, the role of other factors has emerged, including GABA's importance for the maturation of neurons (Nature, 439:589-93, 2006) and the NMDA receptor's regulation of the survival of new neurons (Nature, 442:929-33, 2006).

The holes: "I don't believe the Wnt signaling pathway is the only answer to the mystery of neurogenesis," says Lie. In March this year, Daniel Morris at the Henry Ford Hospital in Detroit and colleagues did not find Wnt upregulated in cells from brains following ischemic stroke, which promotes neurogenesis. "Some of the other pathways could be involved [instead]," says Morris, such as sonic hedgehog or bone morphogenic protein. (Neurosci Lett, 418:170-4, 2007).

The next step: Lie says he's interested in understanding how the neural stem cell and its progeny interpret these various signals. In particular, he's looking for proteins that might coordinate signaling from growth factors and neurotransmitters. "We have all these bits and pieces, but how are they all working together?"