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Distinct contextual roles for Notch signalling in skeletal muscle stem cells - PubMed

️Wed Jan 01 2014

Distinct contextual roles for Notch signalling in skeletal muscle stem cells

Philippos Mourikis et al. BMC Dev Biol. 2014.

Abstract

Notch signalling acts in virtually every tissue during the lifetime of metazoans. Recent studies have pointed to multiple roles for Notch in stem cells during quiescence, proliferation, temporal specification, and maintenance of the niche architecture. Skeletal muscle has served as an excellent paradigm to examine these diverse roles as embryonic, foetal, and adult skeletal muscle stem cells have different molecular signatures and functional properties, reflecting their developmental specification during ontology. Notably, Notch signalling has emerged as a major regulator of all muscle stem cells. This review will provide an overview of Notch signalling during myogenic development and postnatally, and underscore the seemingly opposing contextual activities of Notch that have lead to a reassessment of its role in myogenesis.

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Figures

**Figure 1**
**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, Pax7^Hi 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.

**Figure 2**
**Differential outcomes of loss of Notch activity during regeneration and tissue turnover.** During regeneration (left) both wild type and *Rbpj* null myoblasts proliferate and form new muscle fibres. In the absence of Notch signalling, the size of the amplified population is smaller since the cells fail to self-renew. During tissue homeostasis (right) a small fraction of satellites cells exit quiescence and divide (red chromosomes, BrdU⁺) to give rise to new satellite cells and fusion-competent myoblasts. Satellite cell specific deletion of *Rbpj* results in an increase in the number of cells that exit quiescence; these cells differentiate spontaneously. In sharp contrast to wild type cells the majority of *Rbpj* null satellite cells become Myogenin-positive without going through S-phase (black chromosomes).

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Distinct contextual roles for Notch signalling in skeletal muscle stem cells - PubMed