← Back to Search
Embryonic Myogenesis Pathways In Muscle Regeneration
P. Zhao, E. P. Hoffman
Published 2004 · Biology, Medicine
Download PDFAnalyze on Scholarcy
Embryonic myogenesis involves the staged induction of myogenic regulatory factors and positional cues that dictate cell determination, proliferation, and differentiation into adult muscle. Muscle is able to regenerate after damage, and muscle regeneration is generally thought to recapitulate myogenesis during embryogenesis. There has been considerable progress in the delineation of myogenesis pathways during embryogenesis, but it is not known whether the same signaling pathways are relevant to muscle regeneration in adults. Here, we defined the subset of embryogenesis pathways induced in muscle regeneration using a 27 time‐point in vivo muscle regeneration series. The embryonic Wnt (Wnt1, 3a, 7a, 11), Shh pathway, and the BMP (BMP2, 4, 7) pathway were not induced during muscle regeneration. Moreover, antagonists of Wnt signaling, sFRP1, sFRP2, and sFRP4 (secreted frizzled‐related proteins) were significantly up‐regulated, suggesting active inhibition of the Wnt pathway. The pro‐differentiation FGFR4 pathway was transiently expressed at day 3, commensurate with expression of MyoD, Myogenin, Myf5, and Pax7. Protein verification studies showed fibroblast growth factor receptor 4 (FGFR4) protein to be strongly expressed in differentiating myoblasts and newly formed myotubes. We present evidence that FGF6 is likely the key ligand for FGFR4 during muscle regeneration, and further suggest that FGF6 is released from necrotic myofibers where it is then sequestered by basal laminae. We also confirmed activation of Notch1 in the regenerating muscle. Finally, known MyoD coactivators (MEF2A, p/CIP, TCF12) and repressors (Twist, Id2) were strongly induced at appropriate time points. Taken together, our results suggest that embryonic positional signals (Wnt, Shh, and BMP) are not induced in postnatal muscle regeneration, whereas cell‐autonomous factors (Pax7, MRFs, FGFR4) involving muscle precursor proliferation and differentiation are recapitulated by muscle regeneration. Developmental Dynamics 229:380–392, 2004. © 2004 Wiley‐Liss, Inc.
This paper references
Skeletal muscle regeneration is not impaired in Fgf6 -/- mutant mice.
F. Fiore (2000)
Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells.
D. Cornelison (1997)
Growth factors in skeletal muscle regeneration.
I. Husmann (1996)
Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain
E. Schroeter (1998)
Elevated basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy
P. D'Amore (1994)
Elevated levels of bFGF in the serum of patients with Duchenne muscular dystrophy
PA D’Amore (1994)
Singlecell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle cells
Cornelison DDW (1997)
FGFR4 signaling is a necessary step in limb muscle differentiation.
I. Marics (2002)
The embryonic origin of muscle
S. Hauschka (1994)
smoothened encodes a receptor-like serpentine protein required for hedgehog signalling
M. V. D. Heuvel (1996)
Biochemical evidence that Patched is the Hedgehog receptor
V. Marigo (1996)
Regulation of Pax-3 expression in the dermomyotome and its role in muscle development.
M. Goulding (1994)
Pathophysiology of sodium channelopathies. Studies of sodium channel expression by quantitative multiplex fluorescence polymerase chain reaction.
J. Zhou (1994)
matopoietic potential of stem cells isolated frommurine skeletal muscle
M Kruger (2001)
Identification of skeletal muscle precursor cells in vivo by use of MyoD1 and myogenin probes
M. Grounds (2004)
Muscle regeneration: molecular aspects and therapeutic implications.
M. Grounds (1999)
Cleavage of Chordin by Xolloid Metalloprotease Suggests a Role for Proteolytic Processing in the Regulation of Spemann Organizer Activity
S. Piccolo (1997)
Sonic hedgehog controls epaxial muscle determination through Myf5 activation.
A. Borycki (1999)
Dystrophin expression in the mdx mouse restored by stem cell transplantation
E. Gussoni (1999)
Slug Is a Novel Downstream Target of MyoD
P. Zhao (2002)
Wnt Signaling Induces the Myogenic Specification of Resident CD45+ Adult Stem Cells during Muscle Regeneration
Anna Polesskaya (2003)
The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis.
I. Conboy (2002)
Roles for Proteolysis and Trafficking in Notch Maturation and Signal Transduction
Y. Chan (1998)
The formation of skeletal muscle: from somite to limb
M. Buckingham (2003)
Regulation of dorsal somitic cell fates: BMPs and Noggin control the timing and pattern of myogenic regulator expression.
R. Reshef (1998)
Mox2 is a component of the genetic hierarchy controlling limb muscle development
B. Mankoo (1999)
Sonic hedgehog is a survival factor for hypaxial muscles during mouse development.
M. Krueger (2001)
The tumour-suppressor gene
DM Stone (1996)
A role for FGF-6 in skeletal muscle regeneration.
T. Floss (1997)
Notch signaling: cell fate control and signal integration in development.
S. Artavanis-Tsakonas (1999)
The PEPR GeneChip data warehouse, and implementation of a dynamic time series query tool (SGQT) with graphical interface
J. Chen (2004)
Developmental and functional adaptation of contractile proteins in cardiac and skeletal muscles.
B. Swynghedauw (1986)
Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification.
M. Gustafsson (2002)
The satellite cell and muscle regeneration
R. Bischoff (1994)
The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog
D. M. Stone (1996)
Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5.
S. Tajbakhsh (1998)
Redefining the Genetic Hierarchies Controlling Skeletal Myogenesis: Pax-3 and Myf-5 Act Upstream of MyoD
S. Tajbakhsh (1997)
Muscle regeneration in amphibians and mammals: Passing the torch
B. Carlson (2003)
Hematopoietic potential of stem cells isolated from murine skeletal muscle.
K. Jackson (1999)
The importance of timing differentiation during limb muscle development
H. Amthor (1998)
Expression Profiling in the Muscular Dystrophies Identification of Novel Aspects of Molecular Pathophysiology
Yi-Wen Chen (2000)
Pax7 Is Required for the Specification of Myogenic Satellite Cells
P. Seale (2000)
Delta 1-activated notch inhibits muscle differentiation without affecting Myf5 and Pax3 expression in chick limb myogenesis.
M. Delfini (2000)
In vivo filtering of in vitro MyoD target data: An approach for identification of biologically relevant novel downstream targets of transcription factors (2003)
P. Zhao (2005)
Noggin acts downstream of Wnt and Sonic Hedgehog to antagonize BMP4 in avian somite patterning.
E. Hirsinger (1997)
Regulation of Pax-3 gene expression in the dermomyotome and its role
M Goulding (1994)
Regulation of Pax - 3 gene expression in the dermomyotome and its role in muscle
Differential activation of Myf 5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf 5
S. Tajbakhsh (1998)
This paper is referenced by
Bone Marrow‐Derived Hematopoietic Cells Undergo Myogenic Differentiation Following a Pax‐7 Independent Pathway
Alexandros Xynos (2010)
Characterization of lncRNA–miRNA–mRNA Network to Reveal Potential Functional ceRNAs in Bovine Skeletal Muscle
Binglin Yue (2019)
Embryonic and Adult Stem Cells Explored through Microfluidics and Biological Manipulation
E. Jabart (2013)
Skeletal muscle regeneration in the adult mouse and rat : study on connexin expression and role in normal and regenerating skeletal muscle and on low-intensity endurance exercise effect in damaged skeletal muscles
G. Zummo (2011)
The Roles of the High and Low Molecular Weight Isoforms of Fibroblast Growth Factor 2 in Ischemia-Induced Revascularization
A. Adeyemo (2016)
Early post-hatch fasting induces satellite cell self-renewal.
D. T. Moore (2005)
Talin2 is induced during striated muscle differentiation and is targeted to stable adhesion complexes in mature muscle.
Melissa A Senetar (2007)
CHARACTERIZING THE FUNCTION OF GAS1 IN MUSCLE STEM CELLS AGING
Liangji Li (2019)
Comparison of Muscle Development in Drosophila and Vertebrates
M. Taylor (2013)
Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling
R. Turk (2005)
Computational analysis of mRNA expression profiling in the inner ear reveals candidate transcription factors associated with proliferation, differentiation, and deafness
Kobi Perl (2018)
Transiently Active Wnt/β-Catenin Signaling Is Not Required but Must Be Silenced for Stem Cell Function during Muscle Regeneration
M. Murphy (2014)
Identification and Characterization of a Mef2 Transcriptional Activator in Schistosome Parasites
John N. Milligan (2012)
The Role of the Regenerating Protein Family on Skeletal Muscle Regeneration
M. Nearing (2013)
Wnt antagonist, secreted frizzled-related protein 1, is involved in prenatal skeletal muscle development and is a target of miRNA-1/206 in pigs
Y. Yang (2015)
Myogenic regulatory factors: The orchestrators of myogenesis after 30 years of discovery
Hasan A Asfour (2018)
Skeletal Muscle Regeneration in Advanced Diabetic Peripheral Neuropathy
Kathryn L. Bohnert (2020)
Muscular dystrophy in the mdx mouse is a severe myopathy compounded by hypotrophy, hypertrophy and hyperplasia
W. Duddy (2015)
BMP signalling in craniofacial development.
Xuguang Nie (2006)
Musculin isoforms and repression of MyoD in muscle regeneration.
P. Zhao (2006)
β-catenin promotes self-renewal of skeletal-muscle satellite cells
Ana Perez-Ruiz (2008)
Regulation of Connexin gene expression during skeletal
K. Willecke (2009)
The Effect of Pax3 Over-expression on Myoblast Function
Erik Brijs (2009)
The ontogeny of delta-like protein 1 messenger ribonucleic acid expression during muscle development and regeneration: comparison of broiler and Leghorn chickens.
J. Shin (2009)
MEF 2 A regulates the Gtl 2-Dio 3 microRNA mega-cluster to modulate WNT signaling in skeletal muscle regeneration
Christine M. Snyder ()
Nuclear envelope dystrophies show a transcriptional fingerprint suggesting disruption of Rb-MyoD pathways in muscle regeneration.
M. Bakay (2006)
Genetic loci that regulate healing and regeneration in LG/J and SM/J mice
E. Blankenhorn (2009)
Expression and putative functions of Fibroblast Growth Factor 10 (Fgf10) in developing and adult skeletal muscles
Claire Stratford (2014)
Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program.
M. Lagha (2008)
Thyroid hormone signaling and deiodinase actions in muscle stem/progenitor cells
R. Ambrosio (2017)
Molecular mediators of mesenchymal stem cell biology.
M. Alfaro (2011)
Probe set algorithms: is there a rational best bet?
Jinwook Seo (2006)See more