Fig. 7. Proposed model of modulation of Notch activity by DLL1 shedding during myogenic differentiation. The Notch pathway is active in proliferating Pax7⁺/MyoD⁺ cells derived from Pax7⁺ quiescent satellite cells. Upon exit from the cell cycle, Notch signaling is downregulated in Pax7⁺/MyoD⁺ cells that later become Pax7^–/MyoD⁺, progress into differentiation, and eventually fuse to give rise to myofibers. The level of Notch activity (shown as the yellow gradient) is maintained (or upregulated) in Pax7⁺/MyoD^– cells that replenish the pool of satellite cells. The balance between Pax7⁺/MyoD^– and Pax7⁺/MyoD⁺ cells is maintained by DLL1 shedding by ADAM proteases in a stochastic and cell-density-dependent manner. DLL1 shedding in a pool of cells leads to ligand depletion and downregulation of Notch signaling in neighboring cells, maintenance of MyoD expression, and eventually loss of Pax7 expression. Cells in which DLL1 cleavage takes place acquire higher level of Notch activity than their neighbors, leading to downregulation of MyoD and sustained Pax7 expression.