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.

Macrophage PPARγ, a Lipid Activated Transcription Factor Controls the Growth Factor GDF3 and Skeletal Muscle Regeneration

“…The list of the differentially regulated genes (Fig 7E and Table S2) showed that a limited set of transcripts were either induced or repressed in the presence of GDF3. Several of the differentially regulated genes, including Bex1, (Jiang et al, 2016; Koo et al, 2007), Sgca (Matsumura et al, 1992) and Camk1g, have been implicated in muscle regeneration, muscle structure and/or Ca 2+ homeostasis, showing that macrophage derived GDF3 could elicit biologically relevant changes during muscle regeneration.…”

Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

“…The interplay between death and differentiation signaling is becoming increasingly appreciated (64,(94)(95)(96). Our results showed that Bex1 is highly expressed in early stages of myocardial development and that Bex1 and Tceal8 inhibited cell death in response to ectopic E2f2.…”

“…The endogenous function of Bex/Tceal family proteins are largely unknown, but previous work has shown their role in other cell types such as neuronal differentiation (63) and skeletal myoblast maturation (64,65). BEX1 has been shown to regulate NGF signaling in neurons by altering its activity on p75 NTR and trkA.…”

Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes

“…The endogenous function of Bex/Tceal family proteins are largely unknown, but previous work has shown their role in other cell types such as neuronal differentiation 62 and skeletal myoblast maturation 63,64 . BEX1 has been shown to regulate NGF signaling in neurons by altering its activity on p75 NTR and trkA.…”