Time-lapse analysis and mathematical characterization elucidate novel mechanisms underlying muscle morphogenesis
| Autor: | Clarissa A. Henry, Meghan W. Kelly, Michelle F. Goody, Andre Khalil, Chelsi J. Snow, Robert Jones, Emma C. Oster |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
lcsh:QH426-470 Muscle Fibers Skeletal Cell Biology/Developmental Molecular Mechanisms Morphogenesis 03 medical and health sciences 0302 clinical medicine Laminin Myotome Genetics medicine Image Processing Computer-Assisted Myocyte Animals Muscle Skeletal Molecular Biology Process (anatomy) Genetics (clinical) Ecology Evolution Behavior and Systematics Zebrafish 030304 developmental biology Developmental Biology/Embryology 0303 health sciences biology Myogenesis Developmental Biology/Morphogenesis and Cell Biology Skeletal muscle Models Theoretical Zebrafish Proteins Cell biology Genetics and Genomics/Gene Function Cell Biology/Cell Adhesion lcsh:Genetics medicine.anatomical_structure Biochemistry biology.protein Cell Biology/Morphogenesis and Cell Biology Mathematics/Statistics Elongation 030217 neurology & neurosurgery Research Article |
| Zdroj: | PLoS Genetics, Vol 4, Iss 10, p e1000219 (2008) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | Skeletal muscle morphogenesis transforms short muscle precursor cells into long, multinucleate myotubes that anchor to tendons via the myotendinous junction (MTJ). In vertebrates, a great deal is known about muscle specification as well as how somitic cells, as a cohort, generate the early myotome. However, the cellular mechanisms that generate long muscle fibers from short cells and the molecular factors that limit elongation are unknown. We show that zebrafish fast muscle fiber morphogenesis consists of three discrete phases: short precursor cells, intercalation/elongation, and boundary capture/myotube formation. In the first phase, cells exhibit randomly directed protrusive activity. The second phase, intercalation/elongation, proceeds via a two-step process: protrusion extension and filling. This repetition of protrusion extension and filling continues until both the anterior and posterior ends of the muscle fiber reach the MTJ. Finally, both ends of the muscle fiber anchor to the MTJ (boundary capture) and undergo further morphogenetic changes as they adopt the stereotypical, cylindrical shape of myotubes. We find that the basement membrane protein laminin is required for efficient elongation, proper fiber orientation, and boundary capture. These early muscle defects in the absence of either lamininβ1 or lamininγ1 contrast with later dystrophic phenotypes in lamininα2 mutant embryos, indicating discrete roles for different laminin chains during early muscle development. Surprisingly, genetic mosaic analysis suggests that boundary capture is a cell-autonomous phenomenon. Taken together, our results define three phases of muscle fiber morphogenesis and show that the critical second phase of elongation proceeds by a repetitive process of protrusion extension and protrusion filling. Furthermore, we show that laminin is a novel and critical molecular cue mediating fiber orientation and limiting muscle cell length. Author Summary Despite the importance of muscle fiber development and tendon attachment, this process is incompletely understood in vertebrates. One critical step is muscle fiber elongation; muscle precursor cells are short and subsequent elongation/fusion generates long, multinucleate muscle fibers. Using a vertebrate model organism, the zebrafish, we find that single round myoblasts elongate to span the entire width of the myotome prior to fusion. Using rigorous and objective mathematical characterization techniques, we can further divide muscle development into three stages: short precursor cells, intercalation/elongation, and boundary capture/myotube formation. The second phase, elongation, occurs via a two-step mechanism of protrusion extension and filling. Myotube formation involves boundary capture, where the ends of muscle fibers anchor themselves to the myotome boundary and stop elongating. We show that the protein laminin is required for boundary capture, normal fiber length, and proper fiber orientation. Genetic mosaic experiments in laminin-deficient embryos reveal that boundary capture is a cell autonomous phenomenon. Wild-type (normal) cells capture the boundary appropriately and stop elongating in laminin-deficient embryos. Although adhesion to laminin has been implicated in muscular dystrophies where the attachment between muscle cells and tendons fails, no early developmental requirements for laminin in fast muscle morphogenesis have been shown until now. |
| Databáze: | OpenAIRE |
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