title: The brain expressed x-linked gene 1 (Bex1) regulates myoblast fusion.
abstract: Skeletal muscle development (myogenesis) is a complex but precisely orchestrated process involving spatiotemporal regulation of the proliferation, differentiation and fusion of myogenic progenitor cells (myoblasts). Here we identify brain expressed x-linked gene 1 (Bex1) as a transient, developmentally regulated gene involved in myoblast fusion. Bex1 expression is undetectable in adult muscles or in quiescent muscle stem cells (satellite cells). During embryonic myogenesis, however, Bex1 is robustly expressed by myogenin(+) differentiating myoblasts, but not by Pax7(+) proliferating myoblasts. Interestingly, Bex1 is initially localized in the cytoplasm and then translocates into the nucleus. During adult muscle regeneration, Bex1 is highly expressed in newly regenerated myofibers and the expression is rapidly downregulated during maturation. Consistently, in cultured myoblasts, Bex1 is not expressed at the proliferation stage but transiently expressed upon induction of myogenic differentiation, following a similar cytoplasm to nucleus translocation pattern as seen in vivo. Using gain- and loss-of-function studies, we found that overexpression of Bex1 promotes the fusion of primary myoblasts without affecting myogenic differentiation and myogenin expression. Conversely, Bex1 knockout myoblasts exhibit obvious fusion defects, even though they express normal levels of myogenin and differentiate normally. These results elucidate a novel role of Bex1 in myogenesis through regulating myoblast fusion.
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Yue
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, United States; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, United States. Electronic address: skuang@purdue.edu.
authors.forename: Shihuan
authors.initials: S
authors.lastname: Kuang
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002459:Cell Fusion; D049109:Cell Proliferation; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism
chemical_list: C118512:Bex1 protein, mouse; D009419:Nerve Tissue Proteins
keywords: Myoblasts; Myogenesis; Regeneration; Skeletal muscle