At embryonic stage 10 in the chick, Wise RNA (dark punctate staining) is expressed in the surface ectoderm from the level of the presomitic mesoderm to the posterior end of the embryo. Image courtesy of Nobue Itasaki, National Institute for Medical Research, Mill Hill, London, UK.

The Wnt family of signalling molecules is involved in various aspects of neural development, including the patterning of the nervous system along the anteroposterior (AP) axis. Writing in Development, Itasaki and colleagues report on the identification of a new factor that regulates Wnt signalling, and they show how the consequences of its actions vary for different developmental processes.

The authors carried out a screen to identify factors that can change the AP identity of neural tissue. They 'neuralized' frog animal caps (explants of naive ectoderm) with Noggin, which is an inhibitor of bone morphogenetic protein (BMP) signalling. By default, tissue that is neuralized in this way adopts an anterior character. The authors then looked for factors that are secreted by tissues — such as somites, surface ectoderm or endoderm — that have a posteriorizing effect on neural tissue. A new posteriorizing factor, which they named Wise (Wnt modulator in surface ectoderm), emerged from this screen.

Wise is a secreted molecule that is related to the CCN (Cef10/Cyr61, CTGF and Nov) family of extracellular matrix-associated signalling molecules. When Itasaki et al. overexpressed Wise in animal caps, they found that the tissue acquired a posterior character, as shown by the activation of progressively more posterior markers with increased amounts of Wise. This posteriorizing effect requires Dishevelled and β-catenin, which are components of the canonical Wnt signalling pathway.

The authors then investigated the effects of Wise on another aspect of Wnt function — induction of the neuroaxis. Normally, Wnt8 can induce an entire secondary axis if its RNA is injected into a ventral cell of a 4–8-cell stage frog embryo, but surprisingly, if Wise RNA was injected into the same cell simultaneously, the axis-inducing activity of Wnt8 was inhibited. Interestingly, Wise seems to compete with Wnt8 to bind to lipoprotein receptor-related protein 6 (LRP6), which is a canonical mediator of Wnt signalling.

So, Wise seems to be able to act as an agonist or an inhibitor of Wnt signalling, depending on the cellular context. The next step will be to identify the factors that determine the effects of Wise on the Wnt pathway in these different situations.