scholarly journals Mechanisms of myoblast fusion during muscle development

2015 ◽  
Vol 32 ◽  
pp. 162-170 ◽  
Author(s):  
Ji Hoon Kim ◽  
Peng Jin ◽  
Rui Duan ◽  
Elizabeth H Chen
2020 ◽  
Vol 64 (1-2-3) ◽  
pp. 167-173
Author(s):  
Saroj Jawkar ◽  
Upendra Nongthomba

Myogenesis is a complex multifactorial process leading to the formation of the adult muscle. An amalgamation of autonomous processes including myoblast fusion and myofibrillogenesis, as well as non-autonomous processes, such as innervations from neurons and precise connections with attachment sites, are responsible for successful development and function of muscles. In this review, we describe the development of the indirect flight muscles (IFMs) in Drosophila melanogaster, and highlight the use of the IFMs as a model for studying muscle development and disease, based on recent studies on the development and function of IFMs.


2016 ◽  
Vol 113 (8) ◽  
pp. 2116-2121 ◽  
Author(s):  
Douglas P. Millay ◽  
Dilani G. Gamage ◽  
Malgorzata E. Quinn ◽  
Yi-Li Min ◽  
Yasuyuki Mitani ◽  
...  

During skeletal muscle development, myoblasts fuse to form multinucleated myofibers. Myomaker [Transmembrane protein 8c (TMEM8c)] is a muscle-specific protein that is essential for myoblast fusion and sufficient to promote fusion of fibroblasts with muscle cells; however, the structure and biochemical properties of this membrane protein have not been explored. Here, we used CRISPR/Cas9 mutagenesis to disrupt myomaker expression in the C2C12 muscle cell line, which resulted in complete blockade to fusion. To define the functional domains of myomaker required to direct fusion, we established a heterologous cell–cell fusion system, in which fibroblasts expressing mutant versions of myomaker were mixed with WT myoblasts. Our data indicate that the majority of myomaker is embedded in the plasma membrane with seven membrane-spanning regions and a required intracellular C-terminal tail. We show that myomaker function is conserved in other mammalian orthologs; however, related family members (TMEM8a and TMEM8b) do not exhibit fusogenic activity. These findings represent an important step toward deciphering the cellular components and mechanisms that control myoblast fusion and muscle formation.


2001 ◽  
Vol 153 (4) ◽  
pp. 677-686 ◽  
Author(s):  
Jacqueline Fischer-Lougheed ◽  
Jian-Hui Liu ◽  
Estelle Espinos ◽  
David Mordasini ◽  
Charles R. Bader ◽  
...  

Myoblast fusion is essential to skeletal muscle development and repair. We have demonstrated previously that human myoblasts hyperpolarize, before fusion, through the sequential expression of two K+ channels: an ether-à-go-go and an inward rectifier. This hyperpolarization is a prerequisite for fusion, as it sets the resting membrane potential in a range at which Ca2+ can enter myoblasts and thereby trigger fusion via a window current through α1H T channels.


1960 ◽  
Vol 7 (3) ◽  
pp. 559-565 ◽  
Author(s):  
Charles R. Capers

Healthy, mature, spontaneously contracting muscle was cultivated from explants of 13-day chick embryos for periods up to 4 months in the multipurpose chamber (Rose, 1954) using cellophane-strip technique (Rose et al., 1958) with silicone gaskets, Eagle's medium including 10 per cent horse serum reinforced with 300 mg-per cent of glucose, and the teased type of explant. This method provided optically ideal conditions for the study of muscle fibers with oil immersion, phase contrast time-lapse cinematography at 1 frame per minute without apparent damage for periods as long as 10 days. In no case was mitosis, amitosis, or nuclear "budding" observed in the course of muscle development. Multinuclear muscle fibers have been shown with cine technique to result from both myoblast fusion and polar extension of preformed (explanted) muscle tissue. Myoblast fusion was the only demonstrable way of giving rise to multinucleation. Nuclear membrane "wrinkling" was shown to be merely a temporary distortion that occurred during nuclear migration and rotation. It is suggested that this phenomenon may be responsible for numerous reports of amitosis in the genesis of muscle fibers. The histological development of new straps resulted from an orderly sequence of events. Included in these were polar extension, nuclear migration, rotation, and fixation. Following these events there was increased mitochondrial activity, myofibril formation, and cross-banding. Spontaneous contractions were seen throughout the entire course of differentiation in vitro but became more regular and stronger in the later stages.


2014 ◽  
Vol 46 (12) ◽  
pp. 429-440 ◽  
Author(s):  
Caihong Wei ◽  
Li Li ◽  
Hongwei Su ◽  
Lingyang Xu ◽  
Jian Lu ◽  
...  

It is well known that in sheep most myofibers are formed before birth; however, the crucial myogenic stage and the cellular and molecular mechanisms underpinning phenotypic variation of fetal muscle development remain to be ascertained. We used histological, microarray, and quantitative real-time PCR (qPCR) methods to examine the developmental characteristics of fetal muscle at 70, 85, 100, 120, and 135 days of gestation in sheep. We show that day 100 is an important checkpoint for change in muscle transcriptome and histomorphology in fetal sheep and that the period of 85–100 days is the vital developmental stage for large-scale myoblast fusion. Furthermore, we identified the cis-regulatory motifs for E2F1 or MEF2A in a list of decreasingly or increasingly expressed genes between 85 and 100 days, respectively. Further analysis demonstrated that the mRNA and phosphorylated protein levels of E2F1 and MEF2A significantly declined with myogenic progression in vivo and in vitro. qRT-PCR analysis indicated that PI3K and FST, as targets of E2F1, may be involved in myoblast differentiation and fusion and that downregulation of MEF2A contributes to transition of myofiber types by differential regulation of the target genes involved at the stage of 85–100 days. We clarify for the first time the timing of myofiber proliferation and development during gestation in sheep, which would be beneficial to meat sheep production. Our findings present a repertoire of gene expression in muscle during large-scale myoblast fusion at transcriptome-wide level, which contributes to elucidate the regulatory network of myogenic differentiation.


Author(s):  
R. González Santander ◽  
M.V. Toledo Lobo ◽  
F.J. Martínez Alonso ◽  
G. Martínez Cuadrado ◽  
M. Gánzalez-Santander Martinez ◽  
...  

Muscle fibers are derived from multinucleated myotubes which are themselves formed during embryonic development by the fusion of mononucleated myoblasts. Myoblast fusion results from a sequence of different and highly orchestrated stages demonstrated previously in vitro: recognitionalignment, adhesion and membrane fusion. Like many other fusion systems, myoblast fusion is Ca2+ - dependent. The role of Ca2+ is multiple since it is needed for muscle cell differentiation, for the alignment stage and it has also been demonstrated that Ca2+ influx precedes fusion increasing free intracellular Ca2+. It has been proposed that this increase in free intracellular Ca2+ may activate an enzimatic cascade which leads to membrane fusion.The present study, using the K-pyroantimonate method, describes Ca2+ localization and storage in myoblasts before fusion for the first time, since this method had not been applied to skeletal muscle development studies before. Chick embryos from 51 to 108 h. of incubation (Hamburger and Hamilton stages 16 to 25) were used.


Development ◽  
1981 ◽  
Vol 66 (1) ◽  
pp. 1-26
Author(s):  
B. Woo Youn ◽  
George M. Malacinski

Detailed SEM observations of the changes in cellular morphology, arrangements, and contacts that occur during the process of somite formation were made in two species of urodele amphibians, Ambystoma mexicanum and Pleurodeles waitlii, and one species of anuran amphibian, Rana sphenocephala. After fixation, embryos were fractured transversely, horizontally, and parasagittally, and the intrasomitic cellular arrangement pattern was examined with the SEM. It was found that Ambystoma and Pleurodeles embryos followed exactly the same development sequence in rosette formation and myoblast fusion. Rana somites did not, however, appear to form rosettes. Those myotomal cells underwent fusion immediately after a few segmentations occurred. Patterns of cellular rearrangement were also described during urodele rosette formation at the time of somite segmentation and during myoblast fusion. Extensive changes in cell shape and orientation appeared to occur during those processes. When cells changed their orientation, they often exhibited a triangular configuration. Probable roles of these triangular-shaped cells in rosette formation and myoblast fusion are discussed. During the initial period of myoblast or myotomal cell fusion, cells first send out specialized cell processes and then establish their cell-cell contacts. The establishment of such contacts eventually leads to tight membrane appositions and fusion. Since myoblast fusion appeared to occur between two cells which were tandemly arranged in a rosette, the origin of multinuclearity in the fused cells is discussed. Finally, comparative analyses of the pattern of somite formation and subsequent muscle development were made between different species of amphibians. The possibility is discussed that patterns of somitogenesis may provide useful indicators for determining how different families of amphibians evolved.


2000 ◽  
Vol 10 (17) ◽  
pp. R646-R648 ◽  
Author(s):  
Michael V. Taylor

2015 ◽  
Vol 35 (10) ◽  
pp. 1763-1776 ◽  
Author(s):  
Akiko Suzuki ◽  
Richard C. Pelikan ◽  
Junichi Iwata

Molecules involved in WNT/β-catenin signaling show specific spatiotemporal expression and play vital roles in myogenesis; however, it is still largely unknown how WNT/β-catenin signaling regulates each step of myogenesis. Here, we show that WNT/β-catenin signaling can control diverse biological processes of myogenesis by regulating step-specific molecules. In order to identify the temporally specific roles of WNT/β-catenin signaling molecules in muscle development and homeostasis, we usedin vitroculture systems for both primary mouse myoblasts and C2C12 cells, which can differentiate into myofibers. We found that a blockade of WNT/β-catenin signaling in the proliferating cells decreases proliferation activity, but does not induce cell death, through the regulation of genes cyclin A2 (Ccna2) and cell division cycle 25C (Cdc25c). During muscle differentiation, the inhibition of WNT/β-catenin signaling blocks myoblast fusion through the inhibition of the Fermitin family homolog 2 (Fermt2) gene. Blocking WNT/β-catenin signaling in the well-differentiated myofibers results in the failure of maintenance of their structure by disruption of cadherin/β-catenin/actin complex formation, which plays a crucial role in connecting a myofiber's cytoskeleton to the surrounding extracellular matrix. Thus, our results indicate that WNT/β-catenin signaling can regulate multiple steps of myogenesis, including cell proliferation, myoblast fusion, and homeostasis, by targeting step-specific molecules.


2012 ◽  
Vol 200 (1) ◽  
pp. 109-123 ◽  
Author(s):  
Evgenia Leikina ◽  
Kamran Melikov ◽  
Sarmistha Sanyal ◽  
Santosh K. Verma ◽  
Bokkee Eun ◽  
...  

Myoblast fusion into multinucleated myotubes is a crucial step in skeletal muscle development and regeneration. Here, we accumulated murine myoblasts at the ready-to-fuse stage by blocking formation of early fusion intermediates with lysophosphatidylcholine. Lifting the block allowed us to explore a largely synchronized fusion. We found that initial merger of two cell membranes detected as lipid mixing involved extracellular annexins A1 and A5 acting in a functionally redundant manner. Subsequent stages of myoblast fusion depended on dynamin activity, phosphatidylinositol(4,5)bisphosphate content, and cell metabolism. Uncoupling fusion from preceding stages of myogenesis will help in the analysis of the interplay between protein machines that initiate and complete cell unification and in the identification of additional protein players controlling different fusion stages.


Sign in / Sign up

Export Citation Format

Share Document