Talk:Musculoskeletal System - Muscle Development

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On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2026, August 14) Embryology Musculoskeletal System - Muscle Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Musculoskeletal_System_-_Muscle_Development

2011

Jamb and jamc are essential for vertebrate myocyte fusion

PLoS Biol. 2011 Dec;9(12):e1001216. Epub 2011 Dec 13.

Powell GT, Wright GJ. Source Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.

Abstract

Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both jamb and jamc are dynamically co-expressed in developing muscles and encode receptors that physically interact. Heritable mutations in either gene prevent myocyte fusion in vivo, resulting in an overabundance of mononuclear, but otherwise overtly normal, functional fast-twitch muscle fibres. Transplantation experiments show that the Jamb and Jamc receptors must interact between neighbouring cells (in trans) for fusion to occur. We also show that jamc is ectopically expressed in prdm1a mutant slow muscle precursors, which inappropriately fuse with other myocytes, suggesting that control of myocyte fusion through regulation of jamc expression has important implications for the growth and patterning of muscles. Our discovery of a receptor-ligand pair critical for fusion in vivo has important implications for understanding the molecular mechanisms responsible for myocyte fusion and its regulation in vertebrate myogenesis.

PMID 22180726

The histone methyltransferase Set7/9 promotes myoblast differentiation and myofibril assembly

J Cell Biol. 2011 Aug 22;194(4):551-65.

Tao Y, Neppl RL, Huang ZP, Chen J, Tang RH, Cao R, Zhang Y, Jin SW, Wang DZ. Source McAllister Heart Institute, 2 Department of Cell and Developmental Biology, 3 Department of Biochemistry and Biophysics, 4 Howard Hughes Medical Institute, and 5 Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC 27599. Abstract The molecular events that modulate chromatin structure during skeletal muscle differentiation are still poorly understood. We report in this paper that expression of the H3-K4 histone methyltransferase Set7 is increased when myoblasts differentiate into myotubes and is required for skeletal muscle development, expression of muscle contractile proteins, and myofibril assembly. Knockdown of Set7 or expression of a dominant-negative Set7 mutant impairs skeletal muscle differentiation, accompanied by a decrease in levels of histone monomethylation (H3-K4me1). Set7 directly interacts with MyoD to enhance expression of muscle differentiation genes. Expression of myocyte enhancer factor 2 and genes encoding contractile proteins is decreased in Set7 knockdown myocytes. Furthermore, we demonstrate that Set7 also activates muscle gene expression by precluding Suv39h1-mediated H3-K9 methylation on the promoters of myogenic differentiation genes. Together, our experiments define a biological function for Set7 in muscle differentiation and provide a molecular mechanism by which Set7 modulates myogenic transcription factors during muscle differentiation.

PMID 21859860

Origin of vertebrate limb muscle: the role of progenitor and myoblast populations

Curr Top Dev Biol. 2011;96:1-32.

Murphy M, Kardon G. Source Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA. Abstract Muscle development, growth, and regeneration take place throughout vertebrate life. In amniotes, myogenesis takes place in four successive, temporally distinct, although overlapping phases. Understanding how embryonic, fetal, neonatal, and adult muscle are formed from muscle progenitors and committed myoblasts is an area of active research. In this review we examine recent expression, genetic loss-of-function, and genetic lineage studies that have been conducted in the mouse, with a particular focus on limb myogenesis. We synthesize these studies to present a current model of how embryonic, fetal, neonatal, and adult muscle are formed in the limb.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID 21621065

2010

To build a synapse: signaling pathways in neuromuscular junction assembly

Development. 2010 Apr;137(7):1017-33.

Wu H, Xiong WC, Mei L.

Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. Abstract Synapses, as fundamental units of the neural circuitry, enable complex behaviors. The neuromuscular junction (NMJ) is a synapse type that forms between motoneurons and skeletal muscle fibers and that exhibits a high degree of subcellular specialization. Aided by genetic techniques and suitable animal models, studies in the past decade have brought significant progress in identifying NMJ components and assembly mechanisms. This review highlights recent advances in the study of NMJ development, focusing on signaling pathways that are activated by diffusible cues, which shed light on synaptogenesis in the brain and contribute to a better understanding of muscular dystrophy.

PMID: 20215342 http://www.ncbi.nlm.nih.gov/pubmed/20215342

http://dev.biologists.org/content/137/7/1017.full

Muscle-derived collagen XIII regulates maturation of the skeletal neuromuscular junction

J Neurosci. 2010 Sep 15;30(37):12230-41.

Latvanlehto A, Fox MA, Sormunen R, Tu H, Oikarainen T, Koski A, Naumenko N, Shakirzyanova A, Kallio M, Ilves M, Giniatullin R, Sanes JR, Pihlajaniemi T.

Oulu Center for Cell-Matrix Research, and Department of Medical Biochemistry and Molecular Biology, 90014 University of Oulu, Finland.

Abstract

Formation, maturation, stabilization, and functional efficacy of the neuromuscular junction (NMJ) are orchestrated by transsynaptic and autocrine signals embedded within the synaptic cleft. Here, we demonstrate that collagen XIII, a nonfibrillar transmembrane collagen, is another such signal. We show that collagen XIII is expressed by muscle and its ectodomain can be proteolytically shed into the extracellular matrix. The collagen XIII protein was found present in the postsynaptic membrane and synaptic basement membrane. To identify a role for collagen XIII at the NMJ, mice were generated lacking this collagen. Morphological and ultrastructural analysis of the NMJ revealed incomplete adhesion of presynaptic and postsynaptic specializations in collagen XIII-deficient mice of both genders. Strikingly, Schwann cells erroneously enwrapped nerve terminals and invaginated into the synaptic cleft, resulting in a decreased contact surface for neurotransmission. Consistent with morphological findings, electrophysiological studies indicated both postsynaptic and presynaptic defects in Col13a1(-/-) mice, such as decreased amplitude of postsynaptic potentials, diminished probabilities of spontaneous release and reduced readily releasable neurotransmitter pool. To identify the role of collagen XIII at the NMJ, shed ectodomain of collagen XIII was applied to cultured myotubes, and it was found to advance acetylcholine receptor (AChR) cluster maturation. Together with the delay in AChR cluster development observed in collagen XIII-deficient mutants in vivo, these results suggest that collagen XIII plays an autocrine role in postsynaptic maturation of the NMJ. Altogether, the results presented here reveal that collagen XIII is a novel muscle-derived cue necessary for the maturation and function of the vertebrate NMJ.

PMID: 2084411 http://www.ncbi.nlm.nih.gov/pubmed/20844119

2009

Centrosome proteins - muscle cell differentiation

• Centrosome proteins form an insoluble perinuclear matrix during muscle cell differentiation. Srsen V, Fant X, Heald R, Rabouille C, Merdes A. BMC Cell Biol. 2009 Apr 21;10:28. PMID: 19383121 | BMC Cell Biol.

• Nuclei of non-muscle cells bind centrosome proteins upon fusion with differentiating myoblasts. Fant X, Srsen V, Espigat-Georger A, Merdes A. PLoS One. 2009 Dec 14;4(12):e8303. PMID: 20011525

• Reorganization of microtubule nucleation during muscle differentiation. Bugnard E, Zaal KJ, Ralston E. Cell Motil Cytoskeleton. 2005 Jan;60(1):1-13.PMID: 15532031

Skeletal Dysplasias Associated with Mild Myopathy—A Clinical and Molecular Review

Good figures for bone

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875749/?tool=pubmed

Phenotypes induced by NM causing α-skeletal muscle actin mutants in fibroblasts, Sol 8 myoblasts and myotubes

http://www.biomedcentral.com/1756-0500/2/40/

The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle in zebrafish

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904199

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1904199/pdf/1471-213X-7-54.pdf

Kindlin-2 is required for myocyte elongation and is essential for myogenesis

http://www.biomedcentral.com/1471-2121/9/36

Integrins are required for normal muscle differentiation and disruptions in integrin signaling result in human muscle disease. The intracellular components that regulate integrin function during myogenesis are poorly understood. Unc-112 is an integrin-associated protein required for muscle development in C. elegans. To better understand the intracellular effectors of integrin signaling in muscle, we examined the mammalian homolog of Unc-112, kindlin-2.

Schematic of kindlin-2 function during early myogenesis. A. Undifferentiated C2C12 cells with typical fibroblast-like morphology B. Upon change to differentiation media, control cells withdraw from the cell cycle and elongate. In cells with reduced levels of kindlin-2, cells fail to elongate, and instead maintain a "pro-migratory" phenotype. C. By differentiation day 4, elongated control cells fuse into multinucleated myotubes. Reduced levels of kindlin-2 result in failure of myotube formation, likely as a result of decreased elongation, inadequate cell adhesion and impaired myoblast fusion. One mechanism underlying these alterations is a failure of redistribution of ILK containing focal adhesions.

PITX2 gain-of-function induced defects in mouse forelimb development

http://www.biomedcentral.com/1471-213X/8/25

Extensive molecular differences between anterior- and posterior-half-sclerotomes underlie somite polarity and spinal nerve segmentation

http://www.biomedcentral.com/1471-213X/9/30

We have identified a set of genes that warrant further investigation as regulators of somite polarity and vertebral morphogenesis, as well as repellents of spinal axon growth. Moreover the results indicate that, unlike the posterior half-sclerotome, the central region of the anterior-half-sclerotome does not contribute bone and cartilage to the vertebral column, being associated instead with the development of the segmented spinal nerves.

• Figure 1. Somite patterning and fate. Somite development involves two patterning systems operating along the A-P and D-V axes. (i) Unsegmented presomite mesoderm and nascent somites showing the oscillations and gradients of gene activity that determine A-P polarity prior to overt somite formation (green: anterior half-somite; red: posterior half-somite). (ii) Transverse section through an A-half-epithelial somite (esm, left) and a differentiated somite (right). Patterning along the D-V axis sub-divides the somite into dermatome (dr), myotome (m) and sclerotome (s). The sclerotome is further sub-divided into ventral (v), central (s, red) and (d) dorsal regions. (iii) Representation of two somites viewed laterally, showing the central sclerotome A-P sub-division. Only the anterior-half (green) is permissive for PNS components. (iv) In differentiated vertebrae, posterior-central sclerotomes form the paired transverse processes and pedicles of the neural arches (red) that encase the spinal cord and provide attachment points for epaxial muscles. Anterior central-sclerotome derivatives (green) contribute to peripheral nerve sheaths and prefigure the positions of the intervertebral foraminae (ivf). Spinous process (sp), intervertebral disc (ivd), vertebral body (vb).

© 2009 Hughes et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Glycogenome expression dynamics during mouse C2C12 myoblast differentiation suggests a sequential reorganization of membrane glycoconjugates

Several global transcriptomic and proteomic approaches have been applied in order to obtain new molecular insights on skeletal myogenesis, but none has generated any specific data on glycogenome expression, and thus on the role of glycan structures in this process, despite the involvement of glycoconjugates in various biological events including differentiation and development. In the present study, a quantitative real-time RT-PCR technology was used to profile the dynamic expression of 375 glycogenes during the differentiation of C2C12 myoblasts into myotubes.

http://www.biomedcentral.com/1471-2164/10/483

Nuclear envelope transmembrane proteins (NETs) that are up-regulated during myogenesis

Conclusion: This work identified 6 NETs that are predicted to have important functions in muscle development and/or maintenance from their expression patterns during myoblast differentiation and in mouse tissues. We confirmed that 5 of these NETs are authentic nuclear envelope proteins. Four members of this group have potential signaling functions at the NE, based on their sequence homologies.

http://www.biomedcentral.com/bmccellbiol/imageofthemonth/archive/2006/11

http://www.biomedcentral.com/content/pdf/1471-2121-7-38.pdf

Tendon Development

Genetic analysis of interactions between the somitic muscle, cartilage and tendon cell lineages during mouse development

Development. 2005 Feb;132(3):515-28. Epub 2005 Jan 5.

Brent AE, Braun T, Tabin CJ. Source Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Proper formation of the musculoskeletal system requires the coordinated development of the muscle, cartilage and tendon lineages arising from the somitic mesoderm. During early somite development, muscle and cartilage emerge from two distinct compartments, the myotome and sclerotome, in response to signals secreted from surrounding tissues. As the somite matures, the tendon lineage is established within the dorsolateral sclerotome, adjacent to and beneath the myotome. We examine interactions between the three lineages by observing tendon development in mouse mutants with genetically disrupted muscle or cartilage development. Through analysis of embryos carrying null mutations in Myf5 and Myod1, hence lacking both muscle progenitors and differentiated muscle, we identify an essential role for the specified myotome in axial tendon development, and suggest that absence of tendon formation in Myf5/Myod1 mutants results from loss of the myotomal FGF proteins, which depend upon Myf5 and Myod1 for their expression, and are required, in turn, for induction of the tendon progenitor markers. Our analysis of Sox5/Sox6 double mutants, in which the chondroprogenitors are unable to differentiate into cartilage, reveals that the two cell fates arising from the sclerotome, axial tendon and cartilage are alternative lineages, and that cartilage differentiation is required to actively repress tendon development in the dorsolateral sclerotome.

PMID: 15634692 http://www.ncbi.nlm.nih.gov/pubmed/15634692

Welcome to syndetome: a new somitic compartment

Dev Cell. 2003 May;4(5):611-2.

Dubrulle J, Pourquie O. Source Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. Abstract Virtually nothing was known about the embryonic origin of tendons, until a recent paper by Brent and colleagues in which they track the origin of tendon progenitors of the body axis and reveal the molecular events and tissue interactions leading to their commitment.

Comment on Cell. 2003 Apr 18;113(2):235-48. PMID: 12737797

A somitic compartment of tendon progenitors

Cell. 2003 Apr 18;113(2):235-48.

Brent AE, Schweitzer R, Tabin CJ. Source Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.

Abstract

We demonstrate that the tendons associated with the axial skeleton derive from a heretofore unappreciated, fourth compartment of the somites. Scleraxis (Scx), a bHLH transcription factor, marks this somitic tendon progenitor population at its inception, and is continuously expressed through differentiation into the mature tendons. Two earlier-formed somitic compartments, the sclerotome and myotome, interact to establish this fourth Scx-positive compartment. The tendon progenitors are induced at the sclerotome's edge, at the expense of skeletogenic Pax1 positive cells and in response to FGF signaling in the adjacent myotome. The tendon primordia thus form in a location abutting the two tissues that the mature tendons must ultimately connect. Tendon progenitor formation may reveal a general mechanism for the specification of other somitic subcompartments.

Comment in Dev Cell. 2003 May;4(5):611-2.

PMID: 12705871

http://www.ncbi.nlm.nih.gov/pubmed/12705871

Move this ref to correct page

Fragile X

http://hmg.oxfordjournals.org/content/10/24/2803.full

The RNA-binding Protein Fragile X-related 1 Regulates Somite Formation in Xenopus laevis

http://www.molbiolcell.org/cgi/content/full/16/9/4350

TGF-β

Differentiation plasticity regulated by TGF-β family proteins in development and disease

http://www.nature.com/ncb/journal/v9/n9/full/ncb434.html

PDGF signalling controls the migration of mesoderm cells during chick gastrulation by regulating N-cadherin expression

http://dev.biologists.org/content/135/21/3521.full

Muscle type	Type I	Type IIa	Type IIb
Colour	red	red	white
Shortening speed	slow	fast	fast
Myosin ATPase	slow	intermediate	fast
Fatigue	resistant	intermediate	easily
Metabolism	oxidative	oxidative	glycolytic
Diameter	small	intermediate	large
Sarcoplasmic Reticulum Volume	small	medium	well daveloped
Mitochondria	many	intermediate	few
Lipid droplets	many	intermediate	few
Glycogen	low	intermediate	high
Capillaries	many	intermediate	few
Myoglobin	high	high	low

Neural Crest Cells and Cranial Mesoderm during Head Muscle Development 2009

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0004381

• genetic program controlling head muscle specification is distinct from that underlying trunk and limb myogenesis. Grifone R, Kelly RG (2007) Heartening news for head muscle development. Trends Genet 23: 365–369.
• muscle-independence of tendon initiation and the later muscle requirement for further tendon development is similar to the situation in the limb.
• limb - Scleraxis expression is normally detected in tendon primordia in muscleless limbs in chick and mouse embryos, but is progressively lost in the absence of limb muscles.
• Genetic ablation of Scleraxis in the mouse leads to defective differentiation of limb muscle tendons (no head phenotype has been reported).