THESIS
2021
1 online resource (ix, 69 pages) : illustrations (color)
Abstract
The skeletal muscle is the functional unit of the locomotor apparatus, which enables us to carry out movements and maintain posture. It is made up of myofibres, which are large postmitotic polynucleated cells, that result from the fusion of mononucleated myoblasts. The formation of new myofibres, required during growth or following damage is possible thanks to stem cells called satellite cells. These cells, arrested in G0 phase, are localized in a niche between the basal lamina and the plasmalemma and are recognisable by the presence of Pax7. Studies have been carried out to understand the function of this transcription factor, but its roles and the underlying mechanisms are still not clear. The aim of this thesis project is to investigate the molecular function of Pax7 in adult muscle...[
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The skeletal muscle is the functional unit of the locomotor apparatus, which enables us to carry out movements and maintain posture. It is made up of myofibres, which are large postmitotic polynucleated cells, that result from the fusion of mononucleated myoblasts. The formation of new myofibres, required during growth or following damage is possible thanks to stem cells called satellite cells. These cells, arrested in G0 phase, are localized in a niche between the basal lamina and the plasmalemma and are recognisable by the presence of Pax7. Studies have been carried out to understand the function of this transcription factor, but its roles and the underlying mechanisms are still not clear. The aim of this thesis project is to investigate the molecular function of Pax7 in adult muscle satellite cells. Using an inducible knock out (KO) mouse model for Pax7, we investigated some of the known defects and began to unravel the signalling cascades underlying them. The first defect found was a delay in cell cycle re-entry by quiescent Pax7-null satellite cells upon activation, with a delay regarding both morphological and molecular features. However, most KO Satellite cells were able to re-enter the cell cycle and to divide even though they took longer to complete each cell cycle. This proliferation defect was the result of alteration of multiple cell cycle-related genes including Gadd45, a G2/M arrest gene. In addition, some satellite cells lacking Pax7, were more prone to apoptosis, which was triggered by the extrinsic pathway.Finally, adult Pax7-null satellite cells experienced maintenance defects with their number declining steadily over time. Such a decline in number is unlikely due to precocious differentiation, instead, it was likely caused by enhanced apoptosis seen in Pax7-null satellite cells.
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