Muscle Fiber Diversity Research Articles

Diversité des fibres musculaires squelettiques, rôle des homéoprotéines Six

The mechanisms by which fast/slow muscle fiber diversity emerges during mammalian development are poorly understood, although fast/slow motoneuron activity is known to be an important stimulus controlling fiber-type maintenance and transition in adults. The key role of innervation in the maintenance of the slow-phenotype of the mature adult fibers has been amply demonstrated through denervation and cross-innervation experiments, as well as by the use of various electrical stimulation paradigms. Several signaling pathways have been reported to link nerve stimulation (inducing intracellular calcium elevation) to the maintenance of the slow muscle fiber phenotype. Less is known about the transcription factors and signaling pathways responsible for the fast IIB-glycolytic phenotype. Six1 homeoprotein accumulates at higher levels in the nuclei of adult fast-type myofibers, and Six transcription complexes are far more active in fast/glycolytic fibers than in slow/oxidative fibers. Ectopic expression of Six proteins in the slow soleus muscle leads to a switch from the slow/oxidative phenotype to the fast/glycolytic phenotype, confirming the involvement of this transcriptional complex in the fast/glycolytic phenotype. We have further shown that Six homeoprotein-mutant mice exhibit an impaired capacity to generate fast-type myofibers during embryonic development, and that adult myofibers deprived of Six1 have a slower phenotype. We have also characterized the gene networks controlled by Six homeoproteins at various developmental stages and have shown that, in the adult myofiber, Six proteins control the activity of an enhancer at the fast myosin heavy chain cluster. We identified a three-element genetic partnership in which this enhancer under the control of the myogenic homeoprotein Six1, functions as a regulatory hub that controls the fast fiber phenotype. In this partnership, the enhancer positively controls the expression of both the adjacent fast myosin heavy chain (MYH) gene cluster and Linc-MYH. Linc-MYH is present only in adult fast-type skeletal myofibers, where it suppresses slow-type gene expression.

Fiber Types in Mammalian Skeletal Muscles

Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Analysis of CRE‐mediated recombination driven by myosin light chain 1/3 regulatory elements in embryonic and adult skeletal muscle: A tool to study fiber specification

An increasing number of genes have been implicated in skeletal muscle fiber diversity. To study the contribution of diverse genetic elements to the regulation of fiber-type composition, we generated a transgenic mouse in which CRE recombinase expression is driven by muscle-specific regulatory sequences of the myosin light chain 1/3 locus (MLC). Using ROSA26 conditional reporter mice, we detected expression of the MLC-Cre transgene starting from embryonic day 12.5 (E12.5). By E15, recombination was detected in all muscle-derived structures. Immunohistochemical analysis revealed CRE activity was restricted to fast-twitch (type II) and excluded from slow-twitch (type I) fibers of skeletal muscle. The MLC-Cre transgenic mouse can be used in conjunction with conditional alleles to study both developmental patterning and maintenance of fast fiber-type phenotypes.

Molecular basis of the phenotypic characteristics of mammalian muscle fibres.

Adult mammalian skeletal muscle fibres can be separated into two distinct groups, fast and slow. Within each group there is a continuum of metabolic enzyme activity levels. In addition there are fast and slow isoforms of various myofibrillar proteins such as myosin, tropomyosin and troponin. These proteins are multimeric and multiple isoforms of their subunits assemble to create a continuum of subtypes within each major group. Fibres which coexpress both fast and slow subunit isoforms have an increased number of possible isoform combinations such that an entire spectrum of fibre 'types' is found between the two extremes, fast and slow. Numerous myosin heavy chain and fast troponin T isoforms further increase the diversity of muscle fibres. Such cellular diversity helps to explain the dynamic nature of skeletal muscle. Each individual fibre is able to respond to various functional demands by appropriate changes in its phenotypic expression of specific proteins.

Diversity of muscle fibers in crayfish heart

Diversity of muscle fibers in crayfish heart

Patterns of myosin isoforms in mammalian skeletal muscle fibres.

The present article attempts to combine existing information on the distribution of fast and slow myosin isoforms in histochemically distinct muscle fibres. Four myosin heavy chain (MHC) isoforms, MHCI, MHCIIa, MHCIIb, and MHCIId(x), have been identified in small mammals and have been assigned to the histochemically defined fibre types I, IIA, IIB, and IID(X), respectively. These fibres express only one MHC isoform and are called pure fibre types. Hybrid fibres expressing two MHC isoforms are regarded as transitory between respective pure fibre types. The existence of pure and hybrid fibres even in normal muscles under steady state conditions creates a spectrum of fibre types. The multiplicity of fibre types is even greater when myosin light chains are taken into account. A large number of isomyosins results from the combinatorial patterns of various myosin light and heavy chains isoforms, further increasing the diversity of muscle fibres. As shown by comparative studies, the distribution of different fibre types varies in a muscle-specific, as well as a species-specific manner.

Multiple mechanisms regulate muscle fiber diversity

Adult skeletal muscles are composed of clusters of multinucleated muscle cells called myofibers. At least three different types of myofibers can be detected within mammals based on their physiological properties and their expression of different contractile protein isoforms. Different skeletal muscles display a wide range of combinations of myofibers. Recent work has demonstrated that multiple mechanisms are responsible for the generation of these myofiber types during development. Muscle progenitor cells have been dissected into two categories on the basis of which isoforms of myosin heavy chain (MHC) they express when they differentiate. Neural and other environmental influences act to modify decisions concerning the type of contractile protein a myofiber may express, and this is most apparent for MHC. The other contractile protein gene families are initially regulated independent of the MHC gene family. One or more events late in development are responsible for coordinating isoform expression between the gene families to generate the adult phenotype. Studies of muscle gene expression have revealed that regulation can occur at the levels of transcription, alternative splicing of primary transcripts, mRNA stability, and translation. The current challenge is to decipher how environmental and functional information is interpreted in terms of the activity of the regulators of muscle gene expression.

The Myogenic Lineage: Evidence for Multiple Cellular Precursors during Avian Limb Development

ConclusionsThese studies indicate that there are no generic myoblasts that fuse with other genetic myoblasts to form generic skeletal muscle fibers which then can be molded by the central nervous system into fibers of a variety of types. Experiments on limbs developing aneurally (35, 36) or in which neuromuscular transmission was blocked by curare (3, 37) clearly demonstrated in both instances that muscle fiber diversity proceeded normally. This is most consistent with the diversity of the primary muscle fibers of the limb musculature being rooted in diversity of the myoblast population that produces the first muscle fibers. This is not to say that there is no role for the central nervous system in defining the definitive phenotype of a muscle fiber. Cross-reinnervation experiments as well as analysis of secondary fiber formation in the fetus showed that innervation can modify myosin isoform expression (3, 38, 39). Additional influences such as activity and thyroid hormone exposure can affect the phenotyp...

Heterogeneity of contractile proteins. A continuum of troponin-tropomyosin expression in mammalian skeletal muscle.

Comparison of the myofibrillar proteins from several adult rabbit skeletal muscles has led to the identification of multiple forms of fast and slow troponin T. In Briggs et al. (Briggs, M. M., Klevit, R., and Schachat, F. H. (1984) J. Biol. Chem. 259, 10369-10375) two species of rabbit fast skeletal muscle troponin T (TnT), TnT1f and TnT2f, were characterized. Here, the distribution of these fast TnT species and the alpha- and beta- tropomyosin (Tm) subunits is characterized in fast muscles and in single muscle fibers. Evidence is also presented for two forms of slow skeletal muscle TnT. The presence of each fast TnT species is associated with the presence of a different Tm dimer: TnT1f with alpha beta-Tm and TnT2f with alpha 2-Tm. Histochemical analysis shows that expression of the fast TnT-Tm combinations is not due to differences in the distribution of fast-twitch glycolytic and fast-twitch oxidative-glycolytic fiber types. The absence of a correlation between histochemical typing and the composition of the thin filament Ca2+-regulatory complex is more apparent in individual fast muscle fibers where both fast TnT-Tm combinations appear to be expressed in a continuum. The implications of these observations for mammalian skeletal muscle fiber diversity are discussed.

Diversity of muscle fibers in the abdominal dorsal superficial muscles of the hermit crab,Pagurus pollicarus

The dorsal superficial abdominal muscles of the hermit crab,Pagurus pollicarus, are divided into three subregions of muscle fibers with different properties: a lateral group of tonic muscle fibers and two groups of medial muscle fibers, a superficial layer with intermediate properties and a central layer of twitch fibers. Fast muscles like those in the central medial region are not found in homologous muscles of crayfish and lobster. The number of muscle fibers (74) is the same on the two sides, but there is a tendency for there to be larger fibers on the left side. Length-tension measurements in these muscles resemble results obtained from other crustacean muscles despite their modification as part of a hydrostatic skeletal system. It is concluded that muscle fibers in homologous muscles of different species may vary in their contractile properties, the degree of their segregation into discrete sub-regions, laterality, and number.