About half of the human body mass is comprised of skeletal muscles, a component of the musculoskeletal system involved in maintaining body posture, gait and locomotion. Additionally, skeletal muscles have essential function in glucose metabolism and thermoregulation. Thus, maintenance of skeletal muscle homeostasis is critical for the health of organisms. Satellite cells are muscle-specific stem cells responsible for postnatal growth, regeneration upon injury, and maintenance of skeletal muscle homeostasis. Satellite cell's activity is regulated by a sophisticated network of signalling pathways, which act in a combinatorial manner to regulate satellite cell expansion and differentiation, and to preserve a pool of stem cells during the life course of skeletal muscles. Many of these signalling pathways are known to operate during embryonic myogenesis and are re-activated in adult myogenesis. One such signalling pathway, Sonic hedgehog (Shh) signalling, controls several aspects of myogenesis in the embryo and previous studies have indicated that it plays a role in adult myogenesis. However, it remains unclear whether Shh signalling acts upon satellite cells or non-myogenic resident cells. This study builds on previous work in the lab showing that Shh signalling is cell-autonomously required in satellite cells for efficient muscle regeneration. Through a combination of ex vivo and in vivo genetic approaches, I demonstrated that up-regulation of Shh signalling increased the proliferation of satellite cells by accelerating their entry into cell cycle and progression through the cycle program. Up-regulation of Shh signalling in satellite cells altered also the balance between self-renewal and differentiation, by promoting asymmetric cell division at the expense of symmetric cell division. Given the involvement of Shh signalling in tumour development in other systems and in skeletal muscle tumours i.e. Rhabdomyosarcoma (RMS), the present study may provide novel insights into the role of Shh signalling in the pathogenesis of RMS through the deregulation of satellite cell homeostasis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:766579 |
| Date | January 2019 |
| Creators | Mohd Imran, Kamalliawati |
| Contributors | Borycki, Anne-Gaelle |
| Publisher | University of Sheffield |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.whiterose.ac.uk/22909/ |
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