Regulation of slow and fast muscle myofibrillogenesis by Wnt/beta-catenin and myostatin signaling.
Deviation from proper muscle development or homeostasis results in various myopathic conditions. Employing genetic as well as chemical intervention, we provide evidence that a tight regulation of Wnt/beta-catenin signaling is essential for muscle fiber growth and maintenance. In zebrafish embryos, gain-of-Wnt/beta-catenin function results in unscheduled muscle progenitor proliferation, leading to slow and fast muscle hypertrophy accompanied by fast muscle degeneration. The effects of Wnt/beta-catenin signaling on fast muscle hypertrophy were rescued by misexpression of Myostatin or p21(CIP/WAF), establishing an in vivo regulation of myofibrillogenesis by Wnt/beta-catenin signaling and Myostatin. Epistatic analyses suggest a possible genetic interaction between Wnt/beta-catenin and Myostatin in regulation of slow and fast twitch muscle myofibrillogenesis.
Tee
Jin-Ming
JM
Hubrecht Institute for Developmental Biology and Stem Cell Research and University Medical Center, Utrecht, The Netherlands.
van Rooijen
Carina
C
Boonen
Rick
R
Zivkovic
Danica
D
D000818:Animals; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004843:Epistasis, Genetic; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006984:Hypertrophy; D018656:Muscle Fibers, Fast-Twitch / Q000473:pathology*; D018657:Muscle Fibers, Slow-Twitch / Q000473:pathology*; D009132:Muscles / Q000196:embryology*; D055435:Myostatin / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D051176:beta Catenin / Q000378:metabolism*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D055435:Myostatin; D051153:Wnt Proteins; D051176:beta Catenin