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Crosstalk between the myotome and muscle stem cells during the development of the skeletal muscles of the back
Publication . Gonçalves, André Brás; Thorsteinsdóttir, Sólveig; Deries, Marianne
The deep back (or epaxial) muscles of amniotes derive from the transient myotomes, segmented embryonic muscles that develop from the delamination and differentiation of muscle stem cells (MuSCs) from the overlying dermomyotome. During embryonic development, myogenesis is ensured by the activation of key transcription factors: Myf5, Mrf4, MyoD and Myogenin. The main goal of this thesis was to investigate the role of the myotome in epaxial muscle development. In Chapter 2, a technique of culturing mouse embryo explants was developed, which allowed us to study the in vivo ex utero development of the epaxial myotome and its extracellular matrix (ECM). In Chapter 3, we analysed to what extent the myotome is necessary for later epaxial muscle development using the Myf5nlacZ/nlacZ mouse line, in which the absence of Myf5 and Mrf4 results in the lack of an early myotome. We show that one specific epaxial muscle group (the transversospinalis) is able to differentiate through MyoD, while the other three epaxial muscle groups fail to form. Moreover, we show that due to the lack of myotomal factors, the maintenance of the identity of delaminating dermomyotomal MuSCs fails. In Chapter 4, we described the organisation of laminins, fibronectin and tenascin-C ECMs during myotome development showing that each one of these ECMs potentially has a specific spatial relationship with MuSCs. Finally, Chapter 5 focuses on the role of the myotome in the organisation of these same ECMs and its role in tendon development, using Myf5nlacZ/nlacZ mouse embryos. We show that the myotome is necessary to assemble its own matrices, but these are not required for the development of the transversospinalis muscles. The results of this thesis suggest that the transversospinalis muscles have a distinct developmental mechanism from that of the remaining epaxial muscles and we propose that they are evolutionary more recent.
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Fundação para a Ciência e a Tecnologia

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SFRH

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SFRH/BD/90827/2012

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