The kidney comprises functional units known as nephrons, which are made up of specialised epithelial cells. During development, each nephron arises from a pool of stem cells that undergo mesenchymal-to-epithelial transition (MET) in response to signals such as Wnt4 and Wnt9b. Here, Raphael Kopan and co-workers show that Notch pathway activation can replace inductive Wnt signals during this process (see ). Using gene manipulation in cultured kidneys, the researchers show that Notch pathway activation can induce epithelialisation in nephron stem cells but not in the closely related stromal mesenchymal cells. Continued Notch pathway activation following MET directs cells towards a proximal tubule fate. Finally, they report, Notch-induced MET can occur in the absence of Wnt4 and Wnt9b, suggesting that nephron stem cells are poised to undergo MET, which requires a permissive signal that can be provided by Wnts or by Notch pathway activation. These studies shed new light on our understanding of the early cell fate decisions that are made during kidney development.
