Membrane-myofibril cross-talk in myofibrillogenesis and in muscular dystrophy pathogenesis: lessons from the zebrafish.
Striated muscle has a highly ordered structure in which specialized domains of the cell membrane involved in force transmission (costameres) and excitation-contraction coupling (T tubules) as well as the internal membranes of the sarcoplasmic reticulum are organized over specific regions of the sarcomere. Optimal muscle function is dependent on this high level of organization but how it established and maintained is not well understood. Due to its ex utero development and transparency, the zebrafish embryo is an excellent vertebrate model for the study of dynamic relationships both within and between cells during development. Transgenic models have allowed the delineation of cellular migration and complex morphogenic rearrangements during the differentiation of skeletal myocytes and the assembly and organization of new myofibrils. Molecular targeting of genes and transcripts has allowed the identification of key requirements for myofibril assembly and organization. With the recent advances in gene editing approaches, the zebrafish will become an increasingly important model for the study of human myopathies and muscular dystrophies. Its high fecundity and small size make it well suited to high-throughput screenings to identify novel pharmacologic and molecular therapies for the treatment of a broad range of neuromuscular conditions. In this review, we examine the lessons learned from the zebrafish model regarding the complex interactions between the sarcomere and the sarcolemma that pattern the developing myocyte and discuss the potential for zebrafish as a model system to examine the pathophysiology of, and identify new treatments for, human myopathies and muscular dystrophies.
Division of Pediatric Cardiology, Department of Pediatrics and Communicable Diseases, University of Michigan Ann Arbor, MI, USA.
Maide Ö
MÖ
Raeker
Pediatric Hematology and Oncology, Department of Pediatrics and Communicable Diseases, University of Michigan Ann Arbor, MI, USA.
Jordan A
JA
Shavit
Division of Pediatric Neurology, Department of Pediatrics, The Hospital for Sick Children Toronto, Ontario, CA, USA.
James J
JJ
Dowling
Department of Molecular and Integrative Physiology, University of Michigan Ann Arbor, MI, USA.
Daniel E
DE
Michele
Division of Pediatric Cardiology, Department of Pediatrics and Communicable Diseases, University of Michigan Ann Arbor, MI, USA.
Mark W
MW
Russell
T tubules; myofibrils; sarcolemma; sarcoplasmic reticulum; skeletal muscle; zebrafish