Talk:Musculoskeletal System - Muscle Development

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Cite this page: Hill, M.A. (2021, April 20) Embryology Musculoskeletal System - Muscle Development. Retrieved from


Muscle Stem Cell Immunostaining

Wang S, Zhang B, Addicks GC, Zhang H, J Menzies K & Zhang H. (2018). Muscle Stem Cell Immunostaining. Curr Protoc Mouse Biol , 8, e47. PMID: 30106515 DOI.

Wang S1, Zhang B1, Addicks GC2, Zhang H3, J Menzies K2,4, Zhang H1. Author information Abstract Muscle stem cells (MuSCs) are essential for maintaining muscle homeostasis by providing progenitor cells for muscle regeneration after injury and in muscular diseases. MuSC properties dynamically change, reflecting physiology or pathological status. For instance, MuSCs are activated after muscle injury, but become exhausted in late stages of Duchenne Muscular Dystrophy (DMD) disease and senescent during aging. Therefore, characterization of MuSCs, including proliferation, activation, senescence, and apoptosis, etc., is very important in applying MuSC knowledge to regenerative medicine, such as in the treatment of DMD and to improve muscle function in aging. Here, we describe a detailed method for characterizing MuSCs in situ using immunostaining techniques in the mouse. This method can also be easily adapted to analyze other skeletal muscle properties. © 2018 by John Wiley & Sons, Inc. KEYWORDS: immunostaining; muscle stem cell (MuSC); skeletal muscle PMID: 30106515 DOI: 10.1002/cpmo.47

Hitherto unknown detailed muscle anatomy in an 8-week-old embryo

J Anat. 2018 May 3. doi: 10.1111/joa.12819. [Epub ahead of print]

Warmbrunn MV1, de Bakker BS1, Hagoort J1, Alefs-de Bakker PB2, Oostra RJ1.


Congenital muscle diseases, such as myopathies or dystrophies, occur relatively frequently, with estimated incidences of up to 4.7 per 100 000 newborns. To diagnose congenital diseases in the early stages of pregnancy, and to interpret the results of increasingly advanced in utero imaging techniques, a profound knowledge of normal human morphological development of the locomotor system and the nervous system is necessary. Muscular development, however, is an often neglected topic or is only described in a general way in embryology textbooks and papers. To provide the required detailed and updated comprehensive picture of embryologic muscular anatomy, three-dimensional (3D) reconstructions were created based on serial histological sections of a human embryo at Carnegie stage 23 (8 weeks of development, crown-rump length of 23.8 mm), using Amira reconstruction software. Reconstructed muscles, tendons, bones and nerves were exported in a 3D-PDF file to permit interactive viewing. Almost all adult skeletal muscles of the trunk and limbs could be individually identified in their relative adult position. The pectoralis major muscle was divided in three separate muscle heads. The reconstructions showed remarkable highly developed extraocular, infrahyoid and suprahyoid muscles at this age but surprisingly also absence of the facial muscles that have been described to be present at this stage of development. The overall stage of muscle development suggests heterochrony of skeletal muscle development. Several individual muscle groups were found to be developed earlier and in more detail than described in current literature. KEYWORDS: 3D-PDF; anatomy; embryology; morphogenesis; muscle development; ontogeny; three-dimensional reconstruction PMID: 29726018 DOI: 10.1111/joa.12819


Making muscle: skeletal myogenesis in vivo and in vitro

Development. 2017 Jun 15;144(12):2104-2122. doi: 10.1242/dev.151035.

Chal J1,2,3, Pourquié O4,2,3,5.


Skeletal muscle is the largest tissue in the body and loss of its function or its regenerative properties results in debilitating musculoskeletal disorders. Understanding the mechanisms that drive skeletal muscle formation will not only help to unravel the molecular basis of skeletal muscle diseases, but also provide a roadmap for recapitulating skeletal myogenesis in vitro from pluripotent stem cells (PSCs). PSCs have become an important tool for probing developmental questions, while differentiated cell types allow the development of novel therapeutic strategies. In this Review, we provide a comprehensive overview of skeletal myogenesis from the earliest premyogenic progenitor stage to terminally differentiated myofibers, and discuss how this knowledge has been applied to differentiate PSCs into muscle fibers and their progenitors in vitro. © 2017. Published by The Company of Biologists Ltd.

KEYWORDS: Dermomyotome; Embryonic stem cells; Muscle differentiation; Muscular dystrophy; Paraxial mesoderm; Pluripotent stem cells; Skeletal myogenesis; Somite; iPS cells PMID 28634270 DOI: 10.1242/dev.151035


Development of the epaxial muscles in the human embryo

Clin Anat. 2016 Nov;29(8):1031-1045. doi: 10.1002/ca.22775. Epub 2016 Sep 28.

Mekonen HK1, Hikspoors JP1, Mommen G1, Eleonore KÖhler S1, Lamers WH2,3.


Although the intrinsic muscles of the back are defined by their embryological origin and innervation pattern, no detailed study on their development is available. Human embryos (5-10 weeks development) were studied, using Amira3D® reconstruction and Cinema4D® remodeling software for visualization. At Carnegie Stage (CS)15, the epaxial portions of the myotomes became identifiable laterally to the developing vertebrae. At CS16, these portions fused starting cranially to form a longitudinal muscle column, which became innervated by the dorsal branches of the spinal nerves. At CS17, the longitudinal muscle mass segregated into medial and lateral columns (completed at CS18). At CS18, the medial column segregated again into intermediate and medial columns (completed at CS20). The lateral and intermediate columns did not separate in the lower lumbar and sacral regions. Between CS20 and CS23, the cervical portions of the three columns segregated again from lateral to medial resulting ventrolaterally in rod-like continuations of the caudal portions of the columns and dorsomedially in spade-like portions. The observed topography identifies the iliocostalis and splenius as belonging to the lateral column, the longissimus to the intermediate column, and the (semi-)spinalis to the medial column. The medial (multifidus) group acquired its transversospinal course during closure of the vertebral arches in the early fetal period. Hence, the anatomical ontology of the epaxial muscles is determined by craniocaudal and lateromedial gradients in development. Three longitudinal muscle columns, commonly referred to as the erector spinae, form the basic architectural design of the intrinsic muscles of the back. Clin. Anat. 29:1031-1045, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

KEYWORDS: craniocaudal and mediolateral developmental gradients; intrinsic back muscles; longitudinal muscle columns; neural arch closure PMID 27571325 DOI: 10.1002/ca.22775

Carnegie Stage Event
15 myotome epaxial portion identifiable lateral to the developing vertebrae
16 starting cranially portions fuse to form a longitudinal muscle column innervated by the dorsal branches of the spinal nerves.
17 longitudinal muscle mass commences segregation into medial and lateral columns
17 segregation completes and the medial column commences segregation into intermediate and medial columns
17 segregation completes though lateral and intermediate columns do not separate in the lower lumbar and sacral regions.
20 - 23 cervical portion 3 columns segregated again from lateral to medial resulting ventrolaterally in rod-like continuations of the caudal portions of the columns and dorso-medially in spade-like portions
  • lateral column - iliocostalis and splenius
  • intermediate column - longissimus
  • medial column - semi-spinalis
fetal period medial (multifidus) group acquire transversospinal course during vertebral arch closure
Table data[1]


Head muscle development

Results Probl Cell Differ. 2015;56:123-42. doi: 10.1007/978-3-662-44608-9_6.

Tzahor E1.


The developmental paths that lead to the formation of skeletal muscles in the head are distinct from those operating in the trunk. Craniofacial muscles are associated with head and neck structures. In the embryo, these structures derive from distinct mesoderm populations. Distinct genetic programs regulate different groups of muscles within the head to generate diverse muscle specifications. Developmental and lineage studies in vertebrates and invertebrates demonstrated an overlap in progenitor populations derived from the pharyngeal mesoderm that contribute to certain head muscles and the heart. These studies reveal that the genetic program controlling pharyngeal muscles overlaps with that of the heart. Indeed cardiac and craniofacial birth defects are often linked. Recent studies suggest that early chordates, the last common ancestor of tunicates and vertebrates, had an ancestral pharyngeal mesoderm lineage that later during evolution gave rise to both heart and craniofacial structures. This chapter summarizes studies related to the origins, signaling, genetics, and evolution of the head musculature, highlighting its heterogeneous characteristics in all these aspects. PMID: 25344669 DOI: 10.1007/978-3-662-44608-9_6

Development of the ventral body wall in the human embryo

J Anat. 2015 Nov;227(5):673-85. doi: 10.1111/joa.12380.

Mekonen HK1, Hikspoors JP1, Mommen G1, Köhler SE1, Lamers WH1,2.


Migratory failure of somitic cells is the commonest explanation for ventral body wall defects. However, the embryo increases ~ 25-fold in volume in the period that the ventral body wall forms, so that differential growth may, instead, account for the observed changes in topography. Human embryos between 4 and 10 weeks of development were studied, using amira reconstruction and cinema 4D remodeling software for visualization. Initially, vertebrae and ribs had formed medially, and primordia of sternum and hypaxial flank muscle primordium laterally in the body wall at Carnegie Stage (CS)15 (5.5 weeks). The next week, ribs and muscle primordium expanded in ventrolateral direction only. At CS18 (6.5 weeks), separate intercostal and abdominal wall muscles differentiated, and ribs, sterna, and muscles began to expand ventromedially and caudally, with the bilateral sternal bars fusing in the midline after CS20 (7 weeks) and the rectus muscles reaching the umbilicus at CS23 (8 weeks). The near-constant absolute distance between both rectus muscles and approximately fivefold decline of this distance relative to body circumference between 6 and 10 weeks identified dorsoventral growth in the dorsal body wall as determinant of the 'closure' of the ventral body wall. Concomitant with the straightening of the embryonic body axis after the 6th week, the abdominal muscles expanded ventrally and caudally to form the infraumbilical body wall. Our data, therefore, show that the ventral body wall is formed by differential dorsoventral growth in the dorsal part of the body. © 2015 Anatomical Society. KEYWORDS: abdominal muscles; dorsoventral differential growth; infraumbilical body wall; ventral body wall

PMID 26467243

Tbx15 controls skeletal muscle fibre-type determination and muscle metabolism

Nat Commun. 2015 Aug 24;6:8054. doi: 10.1038/ncomms9054.

Lee KY1, Singh MK2,3, Ussar S1,4, Wetzel P5, Hirshman MF1, Goodyear LJ1, Kispert A2, Kahn CR1.


Skeletal muscle is composed of both slow-twitch oxidative myofibers and fast-twitch glycolytic myofibers that differentially impact muscle metabolism, function and eventually whole-body physiology. Here we show that the mesodermal transcription factor T-box 15 (Tbx15) is highly and specifically expressed in glycolytic myofibers. Ablation of Tbx15 in vivo leads to a decrease in muscle size due to a decrease in the number of glycolytic fibres, associated with a small increase in the number of oxidative fibres. This shift in fibre composition results in muscles with slower myofiber contraction and relaxation, and also decreases whole-body oxygen consumption, reduces spontaneous activity, increases adiposity and glucose intolerance. Mechanistically, ablation of Tbx15 leads to activation of AMPK signalling and a decrease in Igf2 expression. Thus, Tbx15 is one of a limited number of transcription factors to be identified with a critical role in regulating glycolytic fibre identity and muscle metabolism.

PMID 26299309

Prmt5 is a regulator of muscle stem cell expansion in adult mice

Nat Commun. 2015 Jun 1;6:7140. doi: 10.1038/ncomms8140.

Zhang T1, Günther S1, Looso M1, Künne C1, Krüger M1, Kim J1, Zhou Y1, Braun T1.


Skeletal muscle stem cells (MuSC), also called satellite cells, are indispensable for maintenance and regeneration of adult skeletal muscles. Yet, a comprehensive picture of the regulatory events controlling the fate of MuSC is missing. Here, we determine the proteome of MuSC to design a loss-of-function screen, and identify 120 genes important for MuSC function including the arginine methyltransferase Prmt5. MuSC-specific inactivation of Prmt5 in adult mice prevents expansion of MuSC, abolishes long-term MuSC maintenance and abrogates skeletal muscle regeneration. Interestingly, Prmt5 is dispensable for proliferation and differentiation of Pax7(+) myogenic progenitor cells during mouse embryonic development, indicating significant differences between embryonic and adult myogenesis. Mechanistic studies reveal that Prmt5 controls proliferation of adult MuSC by direct epigenetic silencing of the cell cycle inhibitor p21. We reason that Prmt5 generates a poised state that keeps MuSC in a standby mode, thus allowing rapid MuSC amplification under disease conditions.

PMID 26028225


Notch regulation of myogenic versus endothelial fates of cells that migrate from the somite to the limb

Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):8844-9. doi: 10.1073/pnas.1407606111. Epub 2014 Jun 3.

Mayeuf-Louchart A1, Lagha M1, Danckaert A2, Rocancourt D1, Relaix F1, Vincent SD1, Buckingham M3.

Abstract Multipotent Pax3-positive (Pax3(+)) cells in the somites give rise to skeletal muscle and to cells of the vasculature. We had previously proposed that this cell-fate choice depends on the equilibrium between Pax3 and Foxc2 expression. In this study, we report that the Notch pathway promotes vascular versus skeletal muscle cell fates. Overactivating the Notch pathway specifically in Pax3(+) progenitors, via a conditional Pax3(NICD) allele, results in an increase of the number of smooth muscle and endothelial cells contributing to the aorta. At limb level, Pax3(+) cells in the somite give rise to skeletal muscles and to a subpopulation of endothelial cells in blood vessels of the limb. We now demonstrate that in addition to the inhibitory role of Notch signaling on skeletal muscle cell differentiation, the Notch pathway affects the Pax3:Foxc2 balance and promotes the endothelial versus myogenic cell fate, before migration to the limb, in multipotent Pax3(+) cells in the somite of the mouse embryo.

PMID 24927569


Development of the platysma muscle and the superficial musculoaponeurotic system (human specimens at 8-17 weeks of development)

ScientificWorldJournal. 2013 Dec 12;2013:716962. doi: 10.1155/2013/716962. eCollection 2013.

De la Cuadra-Blanco C1, Peces-Peña MD2, Carvallo-de Moraes LO3, Herrera-Lara ME2, Mérida-Velasco JR1. Author information


There is controversy regarding the description of the different regions of the face of the superficial musculoaponeurotic system (SMAS) and its relationship with the superficial mimetic muscles. The purpose of this study is to analyze the development of the platysma muscle and the SMAS in human specimens at 8-17 weeks of development using an optical microscope. Furthermore, we propose to study the relationship of the anlage of the SMAS and the neighbouring superficial mimetic muscles. The facial musculature derives from the mesenchyme of the second arch and migrates towards the different regions of the face while forming premuscular laminae. During the 8th week of development, the cervical, infraorbital, mandibular, and temporal laminae are observed to be on the same plane. The platysma muscle derives from the cervical lamina and its mandibular extension enclosing the lower part of the parotid region and the cheek, while the SMAS derives from the upper region. During the period of development analyzed in this study, we have observed no continuity between the anlage of the SMAS and that of the superficial layer of the temporal fascia and the zygomaticus major muscle. Nor have we observed any structure similar to the SMAS in the labial region.

PMID 24396304


Myoblast fusion: lessons from flies and mice

Development. 2012 Feb;139(4):641-56.

Abmayr SM, Pavlath GK. Source Stowers Institute for Medical Research, Kansas City, MO 64110, USA.


The fusion of myoblasts into multinucleate syncytia plays a fundamental role in muscle function, as it supports the formation of extended sarcomeric arrays, or myofibrils, within a large volume of cytoplasm. Principles learned from the study of myoblast fusion not only enhance our understanding of myogenesis, but also contribute to our perspectives on membrane fusion and cell-cell fusion in a wide array of model organisms and experimental systems. Recent studies have advanced our views of the cell biological processes and crucial proteins that drive myoblast fusion. Here, we provide an overview of myoblast fusion in three model systems that have contributed much to our understanding of these events: the Drosophila embryo; developing and regenerating mouse muscle; and cultured rodent muscle cells.

PMID 22274696


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.


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


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

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.


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


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

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

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

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

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

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

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 (, 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.

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.


The differentiation and morphogenesis of craniofacial muscles

Dev Dyn. 2006 May;235(5):1194-218.

Noden DM, Francis-West P. Source Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.


Unraveling the complex tissue interactions necessary to generate the structural and functional diversity present among craniofacial muscles is challenging. These muscles initiate their development within a mesenchymal population bounded by the brain, pharyngeal endoderm, surface ectoderm, and neural crest cells. This set of spatial relations, and in particular the segmental properties of these adjacent tissues, are unique to the head. Additionally, the lack of early epithelialization in head mesoderm necessitates strategies for generating discrete myogenic foci that may differ from those operating in the trunk. Molecular data indeed indicate dissimilar methods of regulation, yet transplantation studies suggest that some head and trunk myogenic populations are interchangeable. The first goal of this review is to present key features of these diversities, identifying and comparing tissue and molecular interactions regulating myogenesis in the head and trunk. Our second focus is on the diverse morphogenetic movements exhibited by craniofacial muscles. Precursors of tongue muscles partly mimic migrations of appendicular myoblasts, whereas myoblasts destined to form extraocular muscles condense within paraxial mesoderm, then as large cohorts they cross the mesoderm:neural crest interface en route to periocular regions. Branchial muscle precursors exhibit yet another strategy, establishing contacts with neural crest populations before branchial arch formation and maintaining these relations through subsequent stages of morphogenesis. With many of the prerequisite stepping-stones in our knowledge of craniofacial myogenesis now in place, discovering the cellular and molecular interactions necessary to initiate and sustain the differentiation and morphogenesis of these neglected craniofacial muscles is now an attainable goal.

(c) 2006 Wiley-Liss, Inc.

PMID 16502415

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Fragile X

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


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

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

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

  • 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).
  1. Mekonen HK, Hikspoors JP, Mommen G, Eleonore KÖhler S & Lamers WH. (2016). Development of the epaxial muscles in the human embryo. Clin Anat , 29, 1031-1045. PMID: 27571325 DOI.