Impaired embryonic motility in dusp27 mutants reveals a developmental defect in myofibril structure

• Published in: Disease models & mechanisms Vol. 7; no. 2; pp. 289 - 298
• Main Authors: Fero, Kandice, Bergeron, Sadie A, Horstick, Eric J, Codore, Hiba, Li, Grace H, Ono, Fumihito, Dowling, James J, Burgess, Harold A
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01.02.2014; The Company of Biologists Limited; The Company of Biologists
• Subjects: Acoustics; Amino Acid Sequence; Animals; Base Sequence; Congenital diseases; Dual-Specificity Phosphatases - chemistry; Dual-Specificity Phosphatases - genetics; Dual-Specificity Phosphatases - metabolism; dusp27; Edema; Embryo, Nonmammalian - drug effects; Embryo, Nonmammalian - enzymology; Embryo, Nonmammalian - pathology; Embryonic Development - drug effects; Embryos; Gene expression; Gene Knockdown Techniques; Genotype & phenotype; Molecular Sequence Data; Morpholinos - pharmacology; Motility; Movement - drug effects; Muscle; Muscle contraction; Muscle Fibers, Fast-Twitch - drug effects; Muscle Fibers, Fast-Twitch - metabolism; Muscle Fibers, Fast-Twitch - pathology; Mutation; Mutation - genetics; Myofibrillogenesis; Myofibrils - drug effects; Myofibrils - pathology; Phosphatase; Resource; Siblings; Swimming; Zebrafish; Zebrafish - embryology; Zebrafish Proteins - chemistry; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; dusp27; Myofibrillogenesis; Zebrafish; Muscle; Motility
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.013235

An essential step in muscle fiber maturation is the assembly of highly ordered myofibrils that are required for contraction. Much remains unknown about the molecular mechanisms governing the formation of the contractile apparatus. We identified an early embryonic motility mutant in zebrafish caused by integration of a transgene into the pseudophosphatase dual specificity phosphatase 27 (dusp27) gene. dusp27 mutants exhibit near complete paralysis at embryonic and larval stages, producing extremely low levels of spontaneous coiling movements and a greatly diminished touch response. Loss of dusp27 does not prevent somitogenesis but results in severe disorganization of the contractile apparatus in muscle fibers. Sarcomeric structures in mutants are almost entirely absent and only rare triads are observed. These findings are the first to implicate a functional role of dusp27 as a gene required for myofiber maturation and provide an animal model for analyzing the mechanisms governing myofibril assembly.