Article

Xirp proteins mark injured skeletal muscle in zebrafish.

Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.
PLoS ONE (Impact Factor: 3.73). 01/2012; 7(2):e31041. DOI: 10.1371/journal.pone.0031041
Source: PubMed

ABSTRACT Myocellular regeneration in vertebrates involves the proliferation of activated progenitor or dedifferentiated myogenic cells that have the potential to replenish lost tissue. In comparison little is known about cellular repair mechanisms within myocellular tissue in response to small injuries caused by biomechanical or cellular stress. Using a microarray analysis for genes upregulated upon myocellular injury, we identified zebrafish Xin-actin-binding repeat-containing protein1 (Xirp1) as a marker for wounded skeletal muscle cells. By combining laser-induced micro-injury with proliferation analyses, we found that Xirp1 and Xirp2a localize to nascent myofibrils within wounded skeletal muscle cells and that the repair of injuries does not involve cell proliferation or Pax7(+) cells. Through the use of Xirp1 and Xirp2a as markers, myocellular injury can now be detected, even though functional studies indicate that these proteins are not essential in this process. Previous work in chicken has implicated Xirps in cardiac looping morphogenesis. However, we found that zebrafish cardiac morphogenesis is normal in the absence of Xirp expression, and animals deficient for cardiac Xirp expression are adult viable. Although the functional involvement of Xirps in developmental and repair processes currently remains enigmatic, our findings demonstrate that skeletal muscle harbours a rapid, cell-proliferation-independent response to injury which has now become accessible to detailed molecular and cellular characterizations.

0 Bookmarks
 · 
168 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Skeletal myogenesis has been and is currently under extensive study in both mammals and teleosts, with the latter providing a good model for skeletal myogenesis because of their flexible and conserved genome. Parallel investigations of muscle studies using both these models have strongly accelerated the advances in the field. However, when transferring the knowledge from one model to the other, it is important to take into account both their similarities and differences. The main difficulties in comparing mammals and teleosts arise from their different temporal development. Conserved aspects can be seen for muscle developmental origin and segmentation, and for the presence of multiple myogenic waves. Among the divergences, many fish have an indeterminate growth capacity throughout their entire life span, which is absent in mammals, thus implying different post-natal growth mechanisms. This review covers the current state of the art on myogenesis, with a focus on the most conserved and divergent aspects between mammals and teleosts.
    Cellular and Molecular Life Sciences CMLS 03/2014; · 5.62 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Regenerative medicine has the promise to alleviate morbidity and mortality caused by organ dysfunction, longstanding injury and trauma. Although regenerative approaches for a few diseases have been highly successful, some organs either do not regenerate well or have no current treatment approach to harness their intrinsic regenerative potential. In this Review, we describe the modeling of human disease and tissue repair in zebrafish, through the discovery of disease-causing genes using classical forward-genetic screens and by modulating clinically relevant phenotypes through chemical genetic screening approaches. Furthermore, we present an overview of those organ systems that regenerate well in zebrafish in contrast to mammalian tissue, as well as those organs in which the regenerative potential is conserved from fish to mammals, enabling drug discovery in preclinical disease-relevant models. We provide two examples from our own work in which the clinical translation of zebrafish findings is either imminent or has already proven successful. The promising results in multiple organs suggest that further insight into regenerative mechanisms and novel clinically relevant therapeutic approaches will emerge from zebrafish research in the future.
    Disease Models and Mechanisms 07/2014; 7(7):769-776. · 4.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Xin actin-binding repeat containing proteins Xin and XIRP2 are exclusively expressed in striated muscle cells, where they are supposed to play an important role in development. In adult muscle, both proteins are concentrated at attachment sites of myofibrils to the membrane. In contrast, during development they are localized to immature myofibrils together with their binding partner filamin C, indicating an involvement of both proteins in myofibril assembly. We have identified the SH3 domains of nebulin and nebulette as novel ligands of proline-rich regions of Xin and XIRP2. Precise binding motifs were mapped, and shown to bind both SH3 domains with micromolar affinity. Co-crystallization of the nebulette SH3 domain with the interacting XIRP2 peptide PPPTLPKPKLPKH revealed selective interactions that conform to class II SH3-domain-binding peptides. Bimolecular fluorescence complementation experiments in cultured muscle cells indicated a temporally restricted interaction of Xin-repeat proteins with nebulin/nebulette during early stages of myofibril development that is lost upon further maturation. In mature myofibrils, this interaction is limited to longitudinally oriented structures associated with myofibril development and remodeling. These data provide new insights in the role of Xin actin-binding repeat containing proteins (together with their interaction partners) in myofibril assembly and after muscle damage.
    Molecular biology of the cell 08/2013; · 5.98 Impact Factor

Full-text (2 Sources)

View
73 Downloads
Available from
Jun 2, 2014

Similar Publications