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dc.contributor.authorMazelet, Lise
dc.date.accessioned2015-09-29T13:21:23Z
dc.date.available2015-09-29T13:21:23Z
dc.date.issued2015-08
dc.identifier.citationMazelet, L. 2015. The role of contraction in skeletal muscle development. Queen Mary university of London.en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/8960
dc.descriptionPhDen_US
dc.description.abstractThe aim of this project was to determine the role of contraction in skeletal muscle development. The role of the initial spontaneous contractions observed in zebrafish embryos from 17 to 24 hours post fertilisation was examined. Genetic and pharmacologic approaches were used to study paralysis-induced disruption of skeletal muscle structure and function and subsequently determine the role of contraction. The structural and functional characteristics of developing skeletal muscles were found to be regulated by a dual mechanism of both movement-dependent and independent processes, in vivo. Novel data demonstrates that contraction controls sarcomere remodelling, namely regulation of actin length, via movement driven localisation of the actin capping protein, Tropmodulin1. Myofibril length was also shown to be linked to the mechanical passive property, stretch, with lengthening leading to an increase of the muscle’s ability to stretch. In addition, myofibril bundling and the myofilament lattice spacing, responsible for active tension generation via cross-bridge formation, were shown to be unaffected by paralysis and thus, movement-independent processes. Furthermore, the mechanism of the contraction-driven myofibril organisation pathway at the focal adhesion complexes (FAC), was shown to be different in zebrafish compared to mammals, with mechanosensing revolving around the Src protein rather than Fak. In summary, the role of contraction was established as a critical driver of myofibril organisation and passive tension in the developing zebrafish skeletal muscle. Passive tension regulates muscle function by determining its operational range ensuring that the needs of locomotion are met. Furthermore, investigation of FAC’s role in the contractiondriven myofibril organisation pathway led to the discovery of a novel function for Src in zebrafish somitogenesis. These two findings (i) that contraction is a driver of myofibril organisation and (ii) that Src is a key protein of the skeletal muscle development provides the potential for new therapeutic approaches in humans.en_US
dc.description.sponsorshipPhysoc; EuFishBioMed; QMULen_US
dc.language.isoenen_US
dc.publisherQueen Mary University of Londonen_US
dc.subjectMedicineen_US
dc.subjectMusclesen_US
dc.subjectSkeletal musclesen_US
dc.subjectZebrafishen_US
dc.titleThe role of contraction in skeletal muscle developmenten_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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