During early mesoderm induction in sea urchin embryos, maternal signalling through the Wnt/β-catenin/TCF pathway activates the expression of endomesodermal genes. It also drives the expression of the Notch ligand Delta,which regulates the formation of mesodermal precursors. However, later on, Wnt signalling is downregulated in the mesodermal precursors. Now, on ,Röttinger and co-workers reveal that the Nemo-like kinase (NLK) acts downstream of Notch/Delta signalling to downregulate TCF activity during mesoderm induction in sea urchin embryos. They show, for example, that the expression of nlk in the mesodermal lineage is regulated by Notch/Delta signalling and that Delta-induced expression of nlkinhibits TCF function in mesodermal lineages. These results and those from other model systems suggest that, through its ability to inhibit TCF, NLK functions as a conserved negative regulator of Wnt signalling during animal development. They also provide intriguing insights into how the Notch/Delta pathway, although initially activated by Wnt signalling, subsequently acts through NLK to downregulate Wnt signalling.
