During skeletal-muscle development and regeneration, myogenic cells can choose one of two fates – to differentiate into mature muscle or to self-renew to maintain the pool of myogenic precursors. It is known that the balance between these two processes is modulated by the Notch signalling pathway in vivo – but how is cell-fate choice ultimately made? On page 3815, Anna Zolkiewska and colleagues use cultured mouse primary myoblasts and C2C12 myogenic cells to address this question. The authors first show that, in these cell types, Notch activity is essential to maintain the expression of the transcription factor Pax7 (a marker of self-renewing cells); moreover, the level of Pax7 is increased when either cell type is co-cultured with cells expressing the Notch ligand Delta-like 1 (DLL1). DLL1 activity is known to be regulated by proteolytic processing (shedding), and the authors demonstrate that the suppression of shedding (by a catalytically inactive mutant of the DLL1-directed protease ADAM12) promotes Notch signalling and inhibits myoblast differentiation. They go on to provide evidence that, in C2C12 cells, the extent of DLL1 shedding can vary within a single culture. Such asymmetry might, they propose, lead to intercellular differences in Notch signalling that help to sustain the balance between self-renewal and differentiation.