Muscle development and regeneration
During embryonic development, cells become committed to the myogenic fate through the activation of myogenic regulatory factors (MRFs) in the mesoderm. Subsequently, the committed cells, or myoblasts, will differentiate into muscle fibres with specified identities and distinct contractile speeds (the so-called slow and fast twitch fibres). In the zebrafish embryo, progenitors of the slow twitch and fast twitch fibres can be identified based on their morphology and positioning. Terminal differentiation of these different fibre types requires the expression of specific isoforms of sarcomeric proteins, such as the myosin light and heavy chains and troponins. Differentiation of both slow and fast fibres depends on MRF activation. Signalling molecules, such as the Fibroblast Growth Factors (FGF) and Hedgehog (HH) are needed to induce muscle development in distinct parts of the myotome, but the molecular mechanisms behind specification of muscle fibres are not fully understood. Adult muscle regeneration and muscle-derived sarcomas also share many aspects of the embryonic myogenesis.
Image: Jonas von Hofsten
Figure. Fast and slow muscle fibres have distinct biochemical and morphological characteristics and express markers unique to their specific fibre identity.
Our research includes studies related to cellular and developmental processes, such as cell fate determination, muscle regeneration and muscle tumours. To gain knowledge about basic mechanisms behind muscle specification is important in order to understand how muscle cells become allocated to a certain fate. The aim of our research is to gain knowledge about the mechanisms behind muscle development, and how different cell types are specified during muscle differentiation and how this relates to mechanisms in regeneration and tumour formation. The zebrafish model system is ideally suited for the genetic analysis of regulatory processes of these events. Using genome-editing approaches to we generate disease models. This, to increase the knowledge about pathologies linked to specific fibre subtypes and cancers, such as rhabdomyosarcomas. We also study how muscle stem cells respond to muscle injuries in vivo.
If you want to know more - or if you are interested to work with us to do a project, a Ph.D program, or a Post Doc - please do not hesitate to get in touch.