Absence of Desmin in Myofibers of the Zebrafish Extraocular Muscles

Abstract

Purpose To study the medial rectus (MR) muscle of zebrafish ( Danio rerio ) with respect to the pattern of distribution of desmin and its correlation to distinct types of myofibers and motor endplates. Methods The MRs of zebrafish were examined using confocal microscopy in whole-mount longitudinal specimens and in cross sections processed for immunohistochemistry with antibodies against desmin, myosin heavy chain isoforms, and innervation markers. Desmin patterns were correlated to major myofiber type and type of innervation. A total of 1382 myofibers in nine MR muscles were analyzed. Results Four distinct desmin immunolabeling patterns were found in the zebrafish MRs. Approximately a third of all slow myofibers lacked desmin, representing 8.5% of the total myofiber population. The adult zebrafish MR muscle displayed en grappe, en plaque, and multiterminal en plaque neuromuscular junctions (NMJs) with intricate patterns of desmin immunolabeling. Conclusions The MRs of zebrafish showed important similarities with the human extraocular muscles with regard to the pattern of desmin distribution and presence of the major types of NMJs and can be regarded as an adequate model to further study the role of desmin and the implications of heterogeneity in cytoskeletal protein composition. Translational Relevance The establishment of a zebrafish model to study the cytoskeleton in muscles that are particularly resistant to muscle disease opens new avenues to understand human myopathies and muscle dystrophies and may provide clues to new therapies.

Cytoskeletal Proteins in Myotendinous Junctions of Human Extraocular Muscles

“… 27 , 28 On the other hand, lateral force transmission across the muscle cell membrane may put different requirements on the myofibers of the EOMs, given that they are surrounded by a very rich connective tissue bed and, in addition, a large number of myofibers have tapered ends, terminating within the muscle itself. 24 , 29 – 32 We recently demonstrated enriched desmin immunoreactivity in the subsarcolemma of EOM myofibers in both human 17 , 18 and zebrafish, 33 with weak or lack of desmin immunoreactivity inside the myofibers. Such strong immunoreactivity for desmin is typically seen at NMJs or MTJs but not seen subsarcolemmally in limb muscles.…”

fhl2bexpression ameliorates muscular dystrophy

“…Slow myofibers are generally found in the most laterally positioned compartments, separated from fast myofibers by a hyperplastic growth zone positioned near the myosepta 35 . Adult zebrafish EOMs also display a distinct location of slow and fast myofibers, although not separated by a myoseptum 20 (Fig. S1G, I).…”

“…Recently, the muscle specific intermediate filament protein Desmin was shown to be naturally lacking in a subset of EOM myofibers in human and zebrafish 20,21 . Additionally, other intermediate filament proteins such as Nestin and Keratin-19 show a complex pattern in human EOM myotendinous junctions 19 .…”

“…Even though EOMs share attributes with other striated skeletal muscles they differ in terms of gene expression and protein content 16,17 as well as neuromuscular and myotendinous junction composition 18,19 . We have previously shown that zebrafish EOMs are a good model to study the cytoskeleton as well as myofiber and neuromuscular junction cytoarchitecture 20 . Recently, the muscle specific intermediate filament protein Desmin was shown to be naturally lacking in a subset of EOM myofibers in human and zebrafish 20,21 .…”

“…We have previously shown that zebrafish EOMs are a good model to study the cytoskeleton as well as myofiber and neuromuscular junction cytoarchitecture 20 . Recently, the muscle specific intermediate filament protein Desmin was shown to be naturally lacking in a subset of EOM myofibers in human and zebrafish 20,21 . Additionally, other intermediate filament proteins such as Nestin and Keratin-19 show a complex pattern in human EOM myotendinous junctions 19 .…”