MyoD−/− Satellite Cells in Single-Fiber Culture Are Differentiation Defective and MRF4 Deficient

Cornelison, D.D.W.; Olwin, Bradley B.; Rudnicki, Michael A.; Wold, B

doi:10.1006/dbio.2000.9682

Cited by 256 publications

(231 citation statements)

References 33 publications

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“…The other primers used have been published. 34,35 All primers were designed to cross an intron/exon boundary. In the case of Arx amplification, 5% DMSO was added to the reaction mix.…”

Section: Methodsmentioning

confidence: 99%

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

Biressi

Messina²,

Collombat

et al. 2007

Cell Death Differ

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Skeletal muscle fibers form in overlapping, but distinct phases that depend on the generation of temporally different lineages of myogenic cells. During primary myogenesis (E10.5-E12.5 in the mouse), embryonic myoblasts fuse homotypically to generate primary fibers, whereas during later development (E14.5-E17.5), fetal myoblasts differentiate into secondary fibers. How these myogenic waves are regulated remains largely unknown. Studies have been hampered by the lack of markers which would distinguish embryonic from fetal myoblast populations. We show here that the homeobox gene Arx is strongly expressed in differentiating embryonic muscle, downstream of myogenic basic helix-loop-helix (bHLH) genes. Its expression progressively decreases during development. When overexpressed in the C2C12 myogenic cell line, Arx enhances differentiation. Accordingly, it stimulates the transcriptional activity from the Myogenin promoter and from multimerized E-boxes when co-expressed with MyoD and Mef2C in CH310T1/2. Furthermore, Arx co-immunoprecipitates with Mef2C, suggesting that it participates in the transcriptional regulatory network acting in embryonic muscle. Finally, embryonic myoblasts isolated from Arx-deficient embryos show a delayed differentiation in vivo together with an enhanced clonogenic capacity in vitro. We propose here that Arx acts as a novel positive regulator of embryonic myogenesis by synergizing with Mef2C and MyoD and by establishing an activating loop with Myogenin.

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“…The other primers used have been published. 34,35 All primers were designed to cross an intron/exon boundary. In the case of Arx amplification, 5% DMSO was added to the reaction mix.…”

Section: Methodsmentioning

confidence: 99%

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

Biressi

Messina²,

Collombat

et al. 2007

Cell Death Differ

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“…Muscle satellite cells are a small population of myogenic stem cells found in skeletal muscle, characterized by the expression of desmin, Pax7, MyoD, Myf5, and M-cadherin (2)(3)(4)(5). Satellite cells are responsible for muscle repair as skeletal muscle stem cells.…”

mentioning

confidence: 99%

Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle

Asakura

Hirai

Kablar

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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107

114

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MyoD is a myogenic master transcription factor that plays an essential role in muscle satellite cell (muscle stem cell) differentiation. To further investigate the function of MyoD in satellite cells, we examined the transplantation of satellite cell-derived myoblasts lacking the MyoD gene into regenerating skeletal muscle. After injection into injured muscle, MyoD ؊/؊ myoblasts engrafted with significantly higher efficiency compared with wild-type myoblasts. In addition, MyoD ؊/؊ myoblast-derived satellite cells were detected underneath the basal lamina of muscle fibers, indicating the self-renewal property of MyoD ؊/؊ myoblasts. To gain insights into MyoD gene deficiency in muscle stem cells, we investigated the pathways regulated by MyoD by GeneChip microarray analysis of gene expression in wild-type and MyoD ؊/؊ myoblasts. MyoD deficiency led to down-regulation of many muscle-specific genes and up-regulation of some stem cell markers. Importantly, in MyoD ؊/؊ myoblasts, many antiapoptotic genes were up-regulated, whereas genes known to execute apoptosis were downregulated. Consistent with these gene expression profiles, MyoD ؊/؊ myoblasts were revealed to possess remarkable resistance to apoptosis and increased survival compared with wild-type myoblasts. Forced expression of MyoD or the proapoptotic protein Puma increased cell death in MyoD ؊/؊ myoblasts. Therefore, MyoD ؊/؊ myoblasts may preserve stem cell characteristics, including their resistance to apoptosis, expression of stem cell markers, and efficient engraftment and contribution to satellite cells after transplantation. Furthermore, our data offer evidence for improved therapeutic stem cell transplantation for muscular dystrophy, in which suppression of MyoD in myogenic progenitors would be beneficial to therapy by providing a selective advantage for the expansion of stem cells.apoptosis ͉ cell therapy ͉ microarrays ͉ muscular dystrophy ͉ satellite cell

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Section: Introductionmentioning

confidence: 95%

“…In addition, muscles from MyoDϪ/Ϫ mutant mice are severely deficient in regenerative capacity after injury, supporting an essential role of MyoD in adult muscle (Megeney et al, 1996). Both in vivo and ex vivo studies using isolated myofibers and primary cultured myoblasts from MyoDϪ/Ϫ mice show that without MyoD, satellite cells undergo enhanced self-renewal rather than giving rise to progeny that can differentiate (Sabourin et al, 1999;Yablonka-Reuveni et al, 1999;Cornelison et al, 2000).To better understand how postnatal skeletal muscle regeneration is controlled, it is essential to investigate the mechanisms that regulate MyoD expression in activated satellite cells, proliferating myoblasts, and postmitotic differentiating myoblasts. Previous studies have shown that a 24-kbp 5Ј-flanking region of mouse and human MyoD is sufficient to recapitulate endogenous MyoD expression during mouse muscle development and in mature postnatal muscles (Chen et al, 1999(Chen et al, , 2001.…”

mentioning

confidence: 95%

Identification of a New Hybrid Serum Response Factor and Myocyte Enhancer Factor 2-binding Element in MyoD Enhancer Required for MyoD Expression during Myogenesis

L’honoré

Rana

Arsic

et al. 2007

MBoC

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MyoD is a critical myogenic factor induced rapidly upon activation of quiescent satellite cells, and required for their differentiation during muscle regeneration. One of the two enhancers of MyoD, the distal regulatory region, is essential for MyoD expression in postnatal muscle. This enhancer contains a functional divergent serum response factor (SRF)-binding CArG element required for MyoD expression during myoblast growth and muscle regeneration in vivo. Electrophoretic mobility shift assay, chromatin immunoprecipitation, and microinjection analyses show this element is a hybrid SRF-and MEF2 Binding (SMB) sequence where myocyte enhancer factor 2 (MEF2) complexes can compete out binding of SRF at the onset of differentiation. As cells differentiate into postmitotic myotubes, MyoD expression no longer requires SRF but instead MEF2 binding to this dual-specificity element. As such, the MyoD enhancer SMB element is the site for a molecular relay where MyoD expression is first initiated in activated satellite cells in an SRF-dependent manner and then increased and maintained by MEF2 binding in differentiated myotubes. Therefore, SMB is a DNA element with dual and stage-specific binding activity, which modulates the effects of regulatory proteins critical in controlling the balance between proliferation and differentiation. INTRODUCTIONSkeletal muscle repair is fulfilled by satellite cells, quiescent myogenic progenitors located between the basement membrane and myofibers in both growing and mature muscle (Mauro, 1961;Schultz et al., 1978;Muir et al., 1965;Bischoff and Heintz 1994;Yablonka-Reuveni, 1995). They undergo mitogenic activation in response to exercise or damageinduced signals proliferate, differentiate, and fuse into preexisting or newly formed myofibers during muscle regeneration (Grounds and Yablonka-Reuveni, 1993;Schultz and McCormick, 1994).Among basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs), MyoD is the earliest to be induced and detected both in vivo upon muscle regeneration with activation of satellite cells and in ex vivo in cell lines derived from such precursors (Fü tchbauer and Westphal, 1992;Grounds et al., 1992). Indeed, after isolation, activated satellite cells enter the cell cycle and express MyoD concomitantly with proliferating cell nuclear antigen (Smith et al., 1994;Yablonka-Reuveni and Rivera, 1994). This finding suggested a possible role for MyoD during satellite cell activation in regeneration (Yablonka-Reuveni and Rivera, 1994;Yablonka-Reuveni et al., 1999). In agreement with this, we have reported an early induction of MyoD 4 -6 h after entry of quiescent myoblasts into the cell cycle . In addition, muscles from MyoDϪ/Ϫ mutant mice are severely deficient in regenerative capacity after injury, supporting an essential role of MyoD in adult muscle (Megeney et al., 1996). Both in vivo and ex vivo studies using isolated myofibers and primary cultured myoblasts from MyoDϪ/Ϫ mice show that without MyoD, satellite cells undergo enhanced self-renewal rather than giving ...

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MyoD−/− Satellite Cells in Single-Fiber Culture Are Differentiation Defective and MRF4 Deficient

Cited by 256 publications

References 33 publications

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

The homeobox gene Arx is a novel positive regulator of embryonic myogenesis

Increased survival of muscle stem cells lacking the MyoD gene after transplantation into regenerating skeletal muscle

Identification of a New Hybrid Serum Response Factor and Myocyte Enhancer Factor 2-binding Element in MyoD Enhancer Required for MyoD Expression during Myogenesis

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