Myoblast fusion into myotubes is one of the crucial steps of skeletal muscle development (myogenesis). The fusion is preceded by specification of a myogenic lineage (mesodermal progenitors) differentiating into myoblasts and is followed by myofiber-type specification and neuromuscular junction formation. Similarly to other processes of myogenesis, the fusion requires a very precise spatial and temporal regulation occuring both during embryonic development as well as regeneration and repair of the muscle. A plethora of genes and their products is involved in regulation of myoblast fusion and a precise multilevel interplay between them is crucial for myogenic cells to fuse. In this review, we describe both cellular events taking place during myoblast fusion (migration, adhesion, elongation, cell-cell recognition, alignment, and fusion of myoblast membranes enabling formation of myotubes) as well as recent findings on mechanisms regulating this process. Also, we present muscle disorders in humans that have been associated with defects in genes involved in regulation of myoblast fusion.
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http://dx.doi.org/10.1016/j.semcdb.2020.02.004 | DOI Listing |
bioRxiv
December 2024
Department of Bioengineering, University of California, Berkeley, CA 94720.
Cell-cell fusion is fundamental to developmental processes such as muscle formation, as well as to viral infections that cause pathological syncytia. An essential step in fusion is close membrane apposition, but cell membranes are crowded with proteins, glycoproteins, and glycolipids, all of which must be cleared before a fusion pore can be nucleated. Here, we find that cell surface crowding drastically reduces fusogenicity in multiple systems, independent of the method for driving fusion.
View Article and Find Full Text PDFElife
December 2024
Translational Cardiology and Functional Genomics, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
The giant striated muscle protein titin integrates into the developing sarcomere to form a stable myofilament system that is extended as myocytes fuse. The logistics underlying myofilament assembly and disassembly have started to emerge with the possibility to follow labeled sarcomere components. Here, we generated the mCherry knock-in at titin's Z-disk to study skeletal muscle development and remodeling.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Gansu Key Laboratory of Herbivorous Animal Biotechnology, Faculty of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China.
Redox Biol
December 2024
Department of Orthopedics, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, School of Medicine, Fuzhou University, Fuzhou, 350001, China. Electronic address:
In aging and metabolic disease, sarcopenic obesity (SO) correlates with intramuscular adipose tissue (IMAT). Using bioinformatics analysis, we found a potential target protein Extended Synaptotagmin 1 (E-syt1) in SO. To investigate the regulatory role of E-syt1 in muscle metabolism, we performed in vivo and in vitro experiments through E-syt1 loss- and gain-of-function on muscle physiology.
View Article and Find Full Text PDFMutations in protein -glucosyltransferase 1 ( ) cause a recessive form of limb-girdle muscular dystrophy (LGMD-R21) associated with reduced satellite cell number and NOTCH1 signaling in adult patient muscles and impaired myogenic capacity of patient-derived muscle progenitors. However, the roles of POGLUT1 in the development, function, and maintenance of satellite cells are not well understood. Here, we show that conditional deletion of mouse in myogenic progenitors leads to early lethality, postnatal muscle growth defects, reduced expression, abnormality in muscle extracellular matrix, and impaired muscle repair.
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