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Stimuli that promote actin polymerization allow for shuttling of MRTFs to the nucleus where they activate serum response factor (SRF), a regulator of actin and other cytoskeletal protein genes. SRF is an essential regulator of skeletal muscle differentiation and numerous components of the muscle sarcomere, but the potential involvement of MRTFs in skeletal muscle development has not been examined. We explored the role of MRTFs in muscle development in vivo by generating mutant mice harboring a skeletal muscle-specific deletion of MRTF-B and a global deletion of MRTF-A. These double knockout (dKO) mice were able to form sarcomeres during embryogenesis. However, the sarcomeres were abnormally small and disorganized, causing skeletal muscle hypoplasia and perinatal lethality. Transcriptome analysis demonstrated dramatic dysregulation of actin genes in MRTF dKO mice, highlighting the importance of MRTFs in actin cycling and myofibrillogenesis. MRTFs were also shown to be necessary for the survival of skeletal myoblasts and for the efficient formation of intact myotubes. Our findings reveal a central role for MRTFs in sarcomere formation during skeletal muscle development and point to the potential involvement of these transcriptional co-activators in skeletal myopathies.<\/jats:p>","DOI":"10.1242\/dev.135855","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T20:48:01Z","timestamp":1467838081000},"page":"2853-2861","source":"Crossref","is-referenced-by-count":45,"title":["Myocardin-related transcription factors are required for skeletal muscle development"],"prefix":"10.1242","volume":"143","author":[{"given":"Bercin K.","family":"Cenik","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center 1 Department of Molecular Biology , , 5323 Harry Hines Boulevard, Dallas, TX 75390\u20139148 ,","place":["USA"]},{"name":"The Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center 2 , 5323 Harry Hines Boulevard, Dallas, TX 75390\u20139148 ,","place":["USA"]},{"name":"Senator Paul D. 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