The Wnt/β-catenin pathway promotes neural progenitor proliferation but can also inhibit neuronal differentiation and be required for neurogenesis. In this issue, two studies shed light on some of the mechanisms that allow Wnt/β-catenin signalling to play such multifaceted roles in neural development.
On , Elisa Martí and colleagues report that sonic hedgehog (Shh) signalling acts upstream of Wnt/β-catenin signalling to regulate neural progenitor proliferation throughout the chick neural tube (NT). Blocking the Shh pathway is known to result in cell cycle arrest throughout the NT. The authors now show that this is also the case for Wnt/β-catenin signalling because blocking the activity of the Wnt/β-catenin pathway lengthens the G1 phase of the cell cycle in chick embryos. They also demonstrate that Shh activity regulates the Wnt-mediated expression of cyclin D1, an important regulator of cell cycle progression at the G1 stage, by controlling the expression of the Wnt-activated transcription factors Tcf3 and Tcf4. In addition, Shh activity also controls the G2 phase of the cell cycle, independently of Wnt/β-catenin signalling, through the regulation of cyclin E2, cyclin A2 and cyclin B2.These findings indicate that Shh and Wnt/β-catenin signalling co-ordinately regulate cell cycle progression in NT progenitors.
On ,Vetter, Harris, Moore and co-workers investigate the role of Wnt/β-catenin signalling in the transition of Xenopus retinal neural progenitor cells from proliferation to differentiation. These authors have previously reported that Wnt/β-catenin signalling, in addition to promoting retinal progenitor proliferation, activates proneural gene expression in the frog retina by inducing the transcription factor Sox2. They now show that both Wnt/β-catenin signalling and Sox2 block retinal neuron differentiation downstream of proneural gene activity by activating Notch. Moreover, Sox2 inhibits Wnt/β-catenin signalling, and Sox2 protein levels are, in turn, suppressed by the proneural transcription factor Xath5. Thus,the authors conclude, the progenitor-to-neuron transition of retinal neural precursors is driven by a directional modular circuit in which each component inhibits the preceding element while activating the next one.
Taken together, the results of these two papers elucidate how Wnt/β-catenin signalling, through context-dependent regulation, governs neural progenitor fate from proliferation through to neuronal differentiation.
