Although the Notch signalling pathway has been previously implicated in mammalian kidney development, its precise role in this organ's development has remained unclear because mice with disrupted Notch signalling die before the kidney develops. On p. 5031, Cheng et al. circumvent this problem by treating mouse organ kidney cultures with an inhibitor of γ-secretase, the enzyme that is required for Notch activation. The mesenchyme-to-epithelium transition occurred as normal in these cultures, but podocytes and proximal tubules failed to form from the renal vesicle where activated Notch is normally detected. Mice null for the presenilins Psen1 and Psen2 also lack γ-secretase activity, and, on p. 5019, Wang et al. report that Psen1/Psen2 double-null mutants have similar kidney defects to those seen by Cheng et al. To make these experiments possible, the double-null mice were rescued from early embryonic lethality by the restricted expression of a human PSEN1 transgene. In a third paper on Notch, Sasamura and co-workers report that, in Drosophila,the O-fucosylation of Notch is essential for its interaction with its receptor, Delta, and suggest that this modification could be a widespread regulatory mechanism in signal-transduction systems (see p. 4785).