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Title: The role of Notch signalling in the regulation and maintenance of the satellite cell compartment of adult skeletal muscle
Author: Sales, Josephine Laura
ISNI:       0000 0001 3546 847X
Awarding Body: Imperial College London (University of London)
Current Institution: Imperial College London
Date of Award: 2007
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The regenerative potential ofadult skeletal muscle is primarily attributed to satellite cells. Normally quiescent, satellite cells are activated 'on demand' to proliferate and differentiate, facilitating growth or repair. Maintenance of the regenerative capacity requires satellite cell replenishment. It has been shown in vitro that activated satellite cells can adopt divergent fates, with most undergoing terminal differentiation, whilst a minority return to quiescence, mediating self-renewal. This occurs in cell clusters, suggesting that cell-cell signalling may direct fate decisions. Notch signalling relies on cell-cell interaction to specify alternate fates in several systems and has been previously implicated in myogenesis. The aim of this project was to investigate the role of Notch signalling in satellite cell regulation and maintenance. Studies were carried out using C2Cl2 cultures as a model of satellite cell specification.When induced to differentiate, most C2C12 myoblasts contribute to differentiated myotubes, but some are retained as undifferentiated reserve cells with a quiescent, satellite cell-like phenotype. This thesis shows that Notch signalling maintains proliferation in myoblasts and inhibits myogenic differentiation in reserve cells via distinct ligand/receptor interactions. Specifically, interaction between Notchl and Jaggedl appears to maintain proliferation, whereas interaction of Notch3 with Delta-like 4 on nascent myotubes specifies a reserve cell phenotype. Evidence consistent with this model was obtained using satellite cells activated on the surface of isolated myofibres and satellite cell-derived primary cultures. Together, the results show that Notch signalling is involved in satellite cell regulation and suggest a mechanism that may specify alternate fates to facilitate stem cell self-renewal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available