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Notch signalling activity during muscle regeneration. Upper panel: In wild type muscle, quiescent, G0-arrested satellite cells have high Notch activity (purple line), which maintains Pax7 and inhibits Myod (indirectly: dotted line) and Myogenin (directly via Hey1) expression. Immediately after activation, satellite cells downregulate Notch activity and express Myod that is required for appropriate Cdc6 expression and S-phase entry. During the amplification phase high Notch activity is restricted to upstream, Pax7Hi cells that remain undifferentiated and self-renew to replenish the satellite cell pool. Notch activation is triggered by Dll1-bearing differentiating myoblasts. Non-muscle cells, like infiltrating inflammatory cells and fibro/adipogenic progenitors could also trigger or influence Notch activation. The expression of Dll ligands by the mature myofibres is likely, but remains to be demonstrated. Lower panel: Rbpj null satellite cells (no Notch activity: dotted purple line) enter the cell cycle normally and start proliferating. Mutant satellite cells differentiate faster (yellow cells) and fail to self-renew.

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