Developmental myosins: expression patterns and functional significance
© Schiaffino et al. 2015
Received: 30 March 2015
Accepted: 27 May 2015
Published: 15 July 2015
Developing skeletal muscles express unique myosin isoforms, including embryonic and neonatal myosin heavy chains, coded by the myosin heavy chain 3 (MYH3) and MYH8 genes, respectively, and myosin light chain 1 embryonic/atrial, encoded by the myosin light chain 4 (MYL4) gene. These myosin isoforms are transiently expressed during embryonic and fetal development and disappear shortly after birth when adult fast and slow myosins become prevalent. However, developmental myosins persist throughout adult stages in specialized muscles, such as the extraocular and jaw-closing muscles, and in the intrafusal fibers of the muscle spindles. These myosins are re-expressed during muscle regeneration and provide a specific marker of regenerating fibers in the pathologic skeletal muscle. Mutations in MYH3 or MYH8 are responsible for distal arthrogryposis syndromes, characterized by congenital joint contractures and orofacial dysmorphisms, supporting the importance of muscle contractile activity and body movements in joint development and in shaping the form of the face during fetal development. The biochemical and biophysical properties of developmental myosins have only partially been defined, and their functional significance is not yet clear. One possibility is that these myosins are specialized in contracting against low loads, and thus, they may be adapted to the prenatal environment, when fetal muscles contract against a very low load compared to postnatal muscles.
KeywordsMuscle development Muscle regeneration Myosin heavy chain Embryonic myosin Neonatal myosin Distal arthrogryposis
MYH and MYL genes expressed in developing mammalian skeletal muscle
Expression in developing muscle
Expression in adult muscle
Myosin heavy chainsa
Embryonic and fetal muscle
Embryonic and fetal muscle
Embryonic and fetal muscle
Type 1 muscle fibers and ventricles
Fetal (human) or early postnatal (mouse) muscle
Type 2A muscle fibers
Late fetal (human) or early postnatal (mouse) muscle
Type 2X muscle fibers
Type 2B muscle fibers
Essential myosin light chainsc
Fetal muscle (mouse: after E15)
Fast muscle (2B > 2A)
Embryonic muscle, heart
Fetal muscle (mouse: after E15)
Slow skeletal muscle and ventricles
Fetal muscle (human)
Slow skeletal muscle, not ventricles, in human, not mouse
Regulatory myosin light chains
Embryonic and fetal muscle
Embryonic and fetal muscle
Slow muscle and ventricles
Identification of developmental myosins in mammalian skeletal muscle
A number of studies in the 1960s and 1970s reported biochemical evidence suggesting that myosins isolated from mammalian embryonic or fetal skeletal muscle differ from adult muscle myosins (see references in [2, 3]). However, Whalen et al.  were the first to provide unambiguous evidence for the existence of distinct developmental myosins. They identified two specific MyHCs, called embryonic and neonatal (also called perinatal) MyHCs, hereafter referred to as MyHC-emb and MyHC-neo, which precede the appearance of adult fast myosins in the developing rat skeletal muscle . The corresponding MYH genes were identified [4, 5] and found to be located in the same chromosomal locus as gene coding for adult fast myosin heavy chains on chromosome 11 (mouse) or 17 (human) . The gene coding for MyHC-neo (MYH8) shows considerable sequence similarity with adult fast MYH genes, whereas the gene coding for MyHC-emb (MYH3) is quite different (see  for a comparative sequence analysis of MYH genes). Embryonic skeletal muscles also contain a unique type of essential MLC, MLC-1emb, encoded by the MYL4 gene, which is also expressed in the developing heart and in adult atrial myocardium but not in adult skeletal muscle [8, 9].
Developmental myosins in other vertebrates
Developmental myosins are also present in other vertebrates, such as birds and fish, although the sarcomeric myosin gene families are still incompletely characterized in these species. The identification of developmental myosins in fish is complicated by the large number of myosin genes, resulting from whole-genome duplication . In the zebrafish embryo, diversification of fast and slow muscle cell lineages occurs very early in development, under the control of specific signaling pathways, leading to regional specification of different fast and slow MyHC isoforms. Three slow-type myosin genes, smyhc1, smyhc2, and smyhc3, that form a tandem array in the genome, show differential expression patterns, with primary slow fibers predominantly expressing smyhc1 and secondary slow fibers, which are formed later in development, expressing smyhc2 and smyhc3 . Six fast-type myosin genes, arranged as triple repeats located in a narrow region on opposite strands of chromosome 5, also display distinct expression patterns in the zebrafish embryo: the genes in group 1 (fmyhc1.1, fmyhc1.2, and fmyhc1.3) are excluded from the tail and the majority of the cranial muscle, whereas the genes in group 2 (fmyhc2.1, fmyhc2.2, and fmyhc2.3) are highly expressed in the cranial muscles .
In birds, three embryonic and one neonatal MyHC have been identified in developing skeletal muscles (reviewed by ). In addition, the myotome and the developing muscles in chick embryo contain three slow-type MyHCs, referred to as SM1 (or MyHC1), SM2 (or MyHC2), and SM3 (or MyHC3), SM3 being also expressed in the atrial myocardium [13, 14]. Ventricular MyHC is also transiently expressed in the embryonic chick skeletal muscles and is re-expressed during muscle regeneration . The expression of slow-type MyHCs occurs in specific skeletal muscles independently of innervation, as a result of the existence of distinct lineages of myogenic precursors (see ). The switching from developmental to adult isoforms also varies in different chicken muscles: a complete switch from embryonic/neonatal-to-adult fast MyHC occurs in the pectoralis muscle, but most other muscles contain embryonic/neonatal isoforms as major components throughout adult stages .
Embryonic and neonatal myosins during rat and mouse muscle development
Embryonic and neonatal myosins have been especially well characterized in developing rat and mouse skeletal muscles. MyHC-emb and MyHC-neo transcripts have been detected by in situ hybridization in the early developmental stages: in the mouse embryo, MyHC-emb is first detected at 9.5 days post coitum (E9.5) and MyHC-neo at E10.5 . The upregulation of these genes is apparently controlled by the activity of the myogenic regulatory factors MyoD and Myf5, involved in muscle commitment and differentiation, as the proximal promoters of developmental myosin genes contain E-boxes responding to MyoD and Myf5 [17, 18]. The developing skeletal muscles also express a myosin indistinguishable from the adult MyHC-slow, coded by MYH7, as determined by analyses at the protein and transcript level . Based on the pattern of reactivity of a number of anti-myosin antibodies, it was suggested that the slow-type MyHC isoforms present in the embryonic muscles are actually different from those present in the adult skeletal muscle ; however, this interpretation has not been confirmed. It was also suggested that the slow-tonic MyHC, first identified in the extraocular muscles and intrafusal fibers of muscle spindles of the adult muscles  and recently found to be coded by the MYH7b gene , is a slow-developmental isoform widely expressed in most embryonic muscles . However, MYH7b transcripts are present at very low levels in embryonic mouse muscle at E12, and MYH7b protein is not detected in embryonic and fetal muscle using a polyclonal antibody specific for the N-terminal domain of MYH7b, except for rare fibers, first identified around E20, destined to become the bag fibers of muscle spindles (see ). In conclusion, available evidence indicates that three MyHCs are present at the protein level in the developing rat and mouse skeletal muscle: MyHC-emb (MYH3), MyHC-neo (MYH8), and MyHC-slow (MYH7). Immunohistochemical studies showed that the pattern of expression of developmental myosins varies in fibers formed at different developmental stages. In rat primary generation fibers, MyHC-emb is co-expressed with MyHC-slow [19, 24], whereas secondary generation fibers express embryonic and neonatal MyHCs . At the later fetal stages, a number of primary generation fibers tend to lose MyHC-slow and acquire MyHC-neo reactivity, while a number of secondary generation fibers in slow muscles stain also for MyHC-slow .
MyHC gene activation during embryonic myogenesis is accompanied by parallel upregulation of MLCs and other contractile protein genes. In situ hybridization studies showed that the transcripts for MLC-1emb (MYL4) are expressed together with MLC-1fast (the major splicing product of the MYL1 gene) beginning in the early developmental stages in the mouse embryonic skeletal muscle; their relative levels are similar at E12.5 but MLC-1fast becomes predominant at E15.5 . MLC-2fast (MYL3) transcripts are also present early in mouse embryogenesis, with variable temporal and spatial patterns of expression in different muscle groups . In contrast, transcripts for MLC-1slow/ventricular (MYL4) and MLC-3fast (another splicing product of the MYL1 gene) are not detectable in the developing muscles before E15 .
Embryonic/neonatal-to-adult myosin switch
Developmental myosins disappear in most skeletal muscles during the early postnatal development concomitantly with the upregulation of adult fast myosins. In the rat leg skeletal muscles, the transcripts for adult fast MyHCs (MyHC-2A, MyHC-2X, and MyHC-2B, coded by MYH2, MYH1, and MYH4, respectively) are first detected few days after birth by in situ hybridization and become predominant during the subsequent weeks . This switch occurs earlier in the mouse skeletal muscles, as small amounts of adult fast myosin transcripts can be detected even before birth using sensitive RNAase protection assays and by in situ hybridization . However, at the protein level, the fast newborn mouse muscles contain essentially MyHC-neo (about 70 %) and MyHC-emb (about 30 %) with traces of MyHC-slow, as determined by high-resolution gel electrophoresis . The timing of embryonic and neonatal myosin downregulation and adult fast myosin upregulation shows significant variation among body muscles, both at the mRNA  and protein level . The elimination of developmental myosin may also vary within the same muscle, for example, neonatal myosin was found to persist longer in type 2A fibers during postnatal development . Interestingly, the timing of downregulation of developmental MyHC isoforms was essentially unchanged in MYH4 (2B) and MYH1 (2X) null mice .
The switch from developmental to adult fast MyHCs seen in rodent fast muscles takes place also in cultured muscle cells. It has been reported that C2C12 muscle cells, when induced to differentiate upon transfer to low serum medium, first express MyHC-emb, MyHC-neo, and MyHC-slow transcripts, starting at day 1 and peaking at day 2–4 then decreasing, whereas MyHC-2A, MyHC-2X, and MyHC-2B transcripts start to increase at day 2–4 and peak by day 8 (the last time point examined) . However, there are controversial results about the MyHC expression pattern in satellite cell cultures from different skeletal muscles (see [33, 34]), and masticatory-specific myosin heavy chain (Myh16) was detected in cultures of cat jaw muscle but not limb muscle, suggesting that muscle cells from jaw-closing muscles are preprogrammed to express these isoforms during myogenesis in vitro .
The developmental switch from developmental to adult MyHCs can be modulated by extrinsic hormonal and neural influences. The embryonic/neonatal-to-adult fast myosin switch is under the control of a thyroid hormone, hyperthyroidism inducing a precocious expression of adult fast myosin heavy chain mRNA and hypothyroidism inducing a delay in this switching [36–38]. In contrast, nerve activity is apparently not necessary for the embryonic/neonatal-to-fast myosin switch [39, 37] but is required to promote the postnatal accumulation of MyHC-slow and the disappearance of MyHC-emb in the slow soleus muscle .
The molecular mechanisms controlling the myosin switch during development remain to be established and probably involve specific regulatory sequences associated with the MYH gene cluster, where MYH genes are arranged in the order: MYH3-MYH2-MYH1-MYH4-MYH8-MYH13. It has been reported that thyroid hormone controls the transition between neonatal and adult fast 2B MyHC by a long non-coding antisense RNA which is transcriptionally regulated during postnatal development and in response to hypothyroidism: this antisense RNA is transcribed from a site within the intergenic region between MYH8 (MyHC-neo) and the closely associated MYH4 (MyHC-2B) gene and appears to mediate the transcriptional repression of the MYH8 gene . A central enhancer located between the MYH3 and MYH2 genes has been recently identified . This enhancer, whose function is controlled by six homeoproteins, acts in cis by upregulating the expression of fast MYH genes (MYH2, MYH1, and MYH4), located downstream of the enhancer, and in trans via a long intergenic non-coding RNA (linc-Myh) to suppress the expression of MYH7 (MyHC-slow) . However, it is not known whether this enhancer is also involved in the regulation of developmental myosin genes, MYH3 and MYH8, thus behaving like a MYH locus control region (LCR) similar to that present in the β-globin locus, or whether other LCRs, associated to the MYH gene cluster, control the developmental MYH switch.
Myosin changes in the developing human skeletal muscle
In the developing human quadriceps, three MLC proteins can be detected by 2D gel electrophoresis between week 7 and 12 . MLC-3fast becomes clearly visible at week 25, when MLC-1emb starts to decrease rapidly. The major change during the third trimester of gestation is the progressive accumulation of the slow isoforms of MLC, so that at birth, the MLC profile is similar to that of adult muscle . MLC-1sa transcripts are also detectable in human skeletal muscles at week 24, though at significantly lower levels compared to adult muscle .
Developmental myosins in adult skeletal muscle
Re-expression of developmental myosins in regenerating muscle
The switch from embryonic/neonatal-to-adult fast myosins in regenerating muscle is independent of innervation, whereas the switch to slow myosin is controlled by slow nerve activity [69, 66, 70]. In an extensively used model, with muscle injury induced by bupivacaine injection in the rat slow soleus muscle, regenerating myofibers express only embryonic and neonatal myosin transcripts at day 2–3 after injury but, at day 4, start to express adult fast myosin mRNAs. However, in the presence of the nerve, the slow myosin is rapidly upregulated and fast myosin transcripts are downregulated, whereas in the absence of the nerve, adult fast myosins continue to accumulate and slow myosin transcripts remain undetectable . This process is mediated by the pattern of nerve activity, as it can be reproduced by electrical stimulation of regenerating muscle using a stimulation pattern that mimics the endogenous slow motor neuron activity . However, regenerating fast and slow muscles respond differently to the same stimulation pattern, supporting the possibility that the embryonic/neonatal-to-adult fast or slow myosin switch reflects the existence of intrinsic differences between satellite cell populations in the various fiber types. This interpretation is consistent with a number of studies on cultured muscle cells; however, this issue is outside the scope of this review.
Human congenital disorders due to mutations of embryonic and neonatal myosins
The crucial role of embryonic and neonatal myosin during human development has more recently been demonstrated by the pathological consequences of MYH3 and MYH8 mutations (see ). Mutations in the MYH3 (MyHC-emb) gene are responsible for some types of distal arthrogryposis (DA) syndromes, congenital disorders characterized by multiple limb contractures . MYH3 gene mutations have been associated with two major DA syndromes, DA2A and DA2B/DA1. Freeman-Sheldon syndrome (FSS, DA2A) is characterized by facial contractures and congenital scoliosis, in addition to contractures of the limbs. This is the most severe of the DA syndromes and patients require nutritional, surgical, and rehabilitative intervention . FSS was also known as the “whistling-face syndrome”, because the lips appear pursed or pinched leaving only a small oral opening. In fact, to date, the only identified cause of FSS is mutation in the MYH3 gene. DA2B (Sheldon-Hall syndrome, SHS) and DA1, which appear to represent the extremes of the same phenotypically variable and genetically heterogeneous condition, can also be due to MYH3 mutations . However, DA2B and DA1 can also be caused by mutations in TNNI2, coding for fast troponin I, TNNT3, coding for fast troponin T, and TPM2, coding for β-tropomyosin.
MYH8 (MyHC-neo) mutations are responsible for another form of distal arthrogryposis (DA7), referred to as the trismus-pseudocamptodactyly syndrome (TPS) because the patients cannot open the mouth fully (trismus) and show an unusual camptodactyly (flexion of the fingers) that is evident only on dorsiflexion of the wrist (i.e., pseudocamptodactyly). In contrast to the large number of MYH3 mutations causing FSS and SHS, only a single MYH8 mutation (R674Q) has been identified in different families with trismus-pseudocamptodactyly syndrome [83, 84]. The affected residue R674, which because of different numbering corresponds to R672 in the MYH3 gene described above, is conserved in different vertebrate species and in different MYH gene coding for sarcomeric myosins. This residue is localized near the ATP binding site and may thus interfere with myosin catalytic activity. In the family described by Veugelers et al. , TPS was found to be associated with manifestations typical of the Carney complex, including the presence of cardiac myxomas, suggesting a possible role of the MYH8 gene in cardiac development. However, this association was not found in the families reported by Toydemir et al. , and TPS was never observed in large collections of Carney complex cases .
How can one explain the congenital contractures induced by mutations in developmental myosins? A plausible interpretation is that MYH3 or MYH8 gene mutations interfere with myosin’s catalytic activity due to the dominant negative effect of the mutated allele, thus causing defects in myofiber force production in utero. Active movements of the embryo are required for the normal development of the joints, as shown by classic studies in the chick embryo [86, 87]. These studies showed that muscle paralysis induced in ovo by neuromuscular blocking agents, such as curare or botulinum toxin, causes arthrogryposis. The orofacial dysmorphisms induced by MYH3 or MYH8 gene mutations might reflect a similar role of the contraction of facial expression muscles in shaping the form of the face during fetal development.
The view that mutations of MYH3 and MYH8 lead to hypocontractility of fetal muscles has received support by two recent findings. First, the alteration of the cross-bridge turnover in patients carrying R672C mutation has been confirmed by a detailed analysis of myofibril and single-fiber mechanics . Second, preliminary results with isolated myosin S1 (subfragment 1), the portion of the myosin molecule comprising the myosin head and lever arm, which is sufficient to drive actin sliding movement in in vitro motility assays, have shown that several kinetic parameters of the cross-bridge cycle are altered in the presence of R672C, R672H, and T178I FSS-causing mutations .
Contractile properties of embryonic and neonatal myosins
The changes due to myosin isoform developmental replacement were studied in rabbit psoas single fibers . At birth, neonatal myosin is predominant and is progressively replaced by adult fast isoforms. The link between myosin isoform replacement and changes in contractile properties, maximum shortening velocity, and ATPase activity has been analyzed in single muscle fibers where MyHC expression was determined by gel electrophoresis. In rabbit psoas, replacement of neonatal MyHC with adult fast, mainly 2X, isoforms is associated with a threefold increase in maximum shortening velocity  (see Fig. 5c). In the rat diaphragm, neonatal myosin is the predominant isoform in the first two weeks after birth, although rarely expressed alone in individual fibers, but more often associated with fast 2A myosin [97–99]. Fibers expressing predominantly neonatal myosin show values of shortening velocity and ATPase activity comparable to slow fibers and much lower than fast 2X and 2B fibers (Fig. 5d). The disappearance of neonatal myosin is associated with an increase in ATP consumption rate  and increase in power output .
The view that, in mammals, neonatal myosin has kinetics similar to 2A myosin but slower than 2X and 2B myosins has received support from the experiments on recombinant human myosin S1 motor domain expressed in C2C12 myotubes . An additional interesting feature emerging from Resnicow et al.  data is that K m values for actin are much greater for developmental than for adult myosins. This suggests even lower values of ATP hydrolysis rate for immature myofibrils in conditions other than maximal actin activation.
The functional features of embryonic myosin are still little known. The study by Resnicow et al., however, shows that the kinetics of embryonic myosin are slower than those of neonatal myosin, both for ATPase rate and for actin filament sliding velocity . Although the interpretation of this result is complicated by the finding that embryonic myosin motor domain did not bind any light chain when expressed in C2C12 myogenic cells, an independent study points to the same conclusion . Purified myosin and intact myofibrils were prepared from human muscle samples obtained from four fetuses of the age of 12–15 weeks post conception. Quantitative PCR and protein analysis showed that MyHC-emb was largely predominant, above 80 % of the total myosin present. Compared to psoas rabbit myosin (likely a mixture of 2X and 2B myosins), the actin filament velocity of the human embryonic myosin was more than three times lower. Taking into account that rabbit myosins are approximately two times as fast as human embryonic muscle myosin(s) , one can assume that gliding speed of actin filaments on human embryonic myosin is at least 1.5 times lower than on fast human myosin.
Intact myofibrils also allowed determination of force and rate of force development and decline. Force developed by myofibrils containing embryonic myosin was found to be more than ten times lower than that developed by adult human myofibrils . No data are available for the ability to develop force of myofibril containing neonatal myosin, but the results obtained on embryonic myosin suggest that the increase of active force during development may be due not only to accumulation of myofibrils in parallel but also to the transition of myosin isoforms.
While the kinetic properties of the contractile response are almost exclusively linked to the MyHC isoforms, the force development might also be significantly affected by other proteins present in the myofibrillar apparatus. Developmental changes in MLC gene expression (see above) may be relevant. In the thin filament, embryonic and neonatal skeletal muscle may also express unique isoforms: for example, cardiac troponin T (TnT) is expressed in embryonic skeletal muscle and unique TnT isoforms, presumably derived by alternative splicing of the fast skeletal muscle TnT gene, are detected in fetal and neonatal muscle .
Functional significance of developmental myosins
One relevant question remains unanswered: what is the advantage (or necessity), if any, of having specific myosin isoforms during muscle development. Two distinct interpretations can be considered. One possibility is that developmental myosins have structural characteristics appropriate for myofibril formation during myogenesis, both in the embryo and during muscle regeneration in the adult. According to the premyofibril model of myofibrillogenesis developed by Sanger from studies in avian cardiac and skeletal muscle cells and recently confirmed in mouse skeletal muscle cells , myofibril assembly in premyofibrils is characterized by bands of class II non-muscle myosin alternating along actin fibers with bands of muscle-specific α-actinin. The transition from the premyofibril to the nascent myofibril is marked by the addition of class II muscle (sarcomeric) myosin, but it is not known whether the presence at this stage of MyHC-emb is an obligatory step for myofibrillogenesis to occur in skeletal muscle cells. Knockout experiments in vivo or knockdown experiments in cultured muscle cells would be required to address this question. It should be stressed that myofibrils essentially identical to those present in skeletal muscle are formed in the absence of MyHC-emb in developing cardiac muscle cells, which contain only MyHC-β/slow and MyHC-α . Knockout or knockdown experiments could also be used to determine whether embryonic and neonatal isoforms have redundant functions, so that one of them is able to fully compensate for the lack of the other.
Another possibility is that embryonic and neonatal myosins have unique properties adapted to the prenatal developmental environment. For example, it is well known that fetal hemoglobin has a greater oxygen affinity than adult hemoglobin due to specific embryonic and fetal globins, whose presence contributes to transplacental oxygen flux in the context of a relative hypoxic intrauterine environment . Developmental switching of contractile proteins might also be affected by oxygen tension. In cardiac muscle, hypoxia was shown to reactivate gene expression programs of early cardiac development, with upregulation of MyHC-slow (MYH7) and downregulation of MyHC-α cardiac (MYH6), both in ventricles from rats exposed to hypobaric hypoxia and in neonatal rat cardiomyocytes incubated in a hypoxic chamber . In cultured skeletal muscle cells, hypoxia was found to stimulate the expression of MyHC-slow via HIF-1α . The developmental switching of troponin I from the slow skeletal to the cardiac isoform, that is known to modulate the calcium sensitivity of the contractile apparatus, has been associated with the greater resistance to hypoxia and acidosis of the fetal and neonatal heart (see ). However, to our knowledge, there is no comparative study on the effect of hypoxia and acidosis on the function of developmental and adult myosins in skeletal muscle. The low ATPase rate typical of neonatal, and even more, embryonic myosin might suggest that these myosin isoforms allow a contractile activity at a very low energetic cost.
An alternative possibility is that load-bearing properties of developmental myosins play an important role in the transitions of myosin during development, as fetal muscles contract against a very low load compared to postnatal muscles . It is tempting to speculate that fetal tendons, joints, and bones require the mechanical stimuli produced by muscle contraction for their correct growth but, at the same time, cannot bear excessive strains, and embryonic myosin might have appropriate properties in this respect. Accordingly, it has been speculated that the persistence of developmental myosins in the extraocular muscles may be related to the fact that oculorotatory muscles contract against a much lower load compared to other skeletal muscles . This interpretation could be tested by specific experimental approaches. In particular, it will be crucial to determine the contractility of embryonic and neonatal myosin by loaded in vitro motility assays and single-molecule analyses with a dual-beam laser trap (see ).
The presence of unique MyHCs and MLCs in developing skeletal muscle and their re-expression in regenerating muscle was first reported in the late 1970s to early 1980s. During the subsequent years, the gene coding for embryonic and neonatal myosins were characterized, their expression patterns were defined, and the factors involved in the developmental-to-adult myosin switch were identified. However, the physiological significance of developmental myosins remained completely unclear until 2006, when embryonic (MYH3) mutations were first reported to cause specific syndromes characterized by congenital joint contractures. This finding has opened up a new phase of research aimed at dissecting the functional properties of embryonic and neonatal myosins and the consequences of their mutations. Analyses on myofibrils and single fibers, and especially on isolated myosin S1, are expected to define the kinetic parameters of the cross-bridge cycle of developmental myosins and their response to loading conditions, thus addressing the unsettled question of why specific myosin isoforms are needed during muscle development.
myosin light chain (protein)
- MYH :
myosin heavy chain (gene)
myosin heavy chain (protein)
- MYL :
myosin light chain (gene)
We thank Prof. Elena Pegoraro for providing the polymyositis biopsy and Irene Moretti and Stefano Ciciliot for the help with the figures.
- Schiaffino S, Reggiani C. Fiber types in mammalian skeletal muscles. Physiol Rev. 2011;91:1447–531.PubMedView ArticleGoogle Scholar
- Whalen RG, Sell SM, Butler-Browne GS, Schwartz K, Bouveret P, Pinset-Harstom I. Three myosin heavy-chain isozymes appear sequentially in rat muscle development. Nature. 1981;292:805–9.PubMedView ArticleGoogle Scholar
- Sartore S, Gorza L, Schiaffino S. Fetal myosin heavy chains in regenerating muscle. Nature. 1982;298:294–6.PubMedView ArticleGoogle Scholar
- Periasamy M, Wieczorek DF, Nadal-Ginard B. Characterization of a developmentally regulated perinatal myosin heavy-chain gene expressed in skeletal muscle. J Biol Chem. 1984;259:13573–8.PubMedGoogle Scholar
- Wydro RM, Nguyen HT, Gubits RM, Nadal-Ginard B. Characterization of sarcomeric myosin heavy chain genes. J Biol Chem. 1983;258:670–8.PubMedGoogle Scholar
- Leinwand LA, Saez L, McNally E, Nadal-Ginard B. Isolation and characterization of human myosin heavy chain genes. Proc Natl Acad Sci U S A. 1983;80:3716–20.PubMed CentralPubMedView ArticleGoogle Scholar
- Weiss A, Schiaffino S, Leinwand LA. Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: implications for functional diversity. J Mol Biol. 1999;290:61–75.PubMedView ArticleGoogle Scholar
- Kurabayashi M, Komuro I, Tsuchimochi H, Takaku F, Yazaki Y. Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones. J Biol Chem. 1988;263:13930–6.PubMedGoogle Scholar
- Whalen RG, Butler-Browne GS, Gros F. Identification of a novel form of myosin light chain present in embryonic muscle tissue and cultured muscle cells. J Mol Biol. 1978;126:415–31.PubMedView ArticleGoogle Scholar
- Ikeda D, Ono Y, Snell P, Edwards YJ, Elgar G, Watabe S. Divergent evolution of the myosin heavy chain gene family in fish and tetrapods: evidence from comparative genomic analysis. Physiol Genomics. 2007;32:1–15.PubMedView ArticleGoogle Scholar
- Elworthy S, Hargrave M, Knight R, Mebus K, Ingham PW. Expression of multiple slow myosin heavy chain genes reveals a diversity of zebrafish slow twitch muscle fibres with differing requirements for Hedgehog and Prdm1 activity. Development. 2008;135:2115–26.PubMedView ArticleGoogle Scholar
- Nord H, Burguiere AC, Muck J, Nord C, Ahlgren U, von Hofsten J. Differential regulation of myosin heavy chains defines new muscle domains in zebrafish. Mol Biol Cell. 2014;25:1384–95.PubMed CentralPubMedView ArticleGoogle Scholar
- Bandman E, Rosser BW. Evolutionary significance of myosin heavy chain heterogeneity in birds. Microsc Res Tech. 2000;50:473–91.PubMedView ArticleGoogle Scholar
- Sacks LD, Cann GM, Nikovits Jr W, Conlon S, Espinoza NR, Stockdale FE. Regulation of myosin expression during myotome formation. Development. 2003;130:3391–402.PubMedView ArticleGoogle Scholar
- Stockdale FE. Myogenic cell lineages. Dev Biol. 1992;154:284–98.PubMedView ArticleGoogle Scholar
- Lyons GE, Ontell M, Cox R, Sassoon D, Buckingham M. The expression of myosin genes in developing skeletal muscle in the mouse embryo. J Cell Biol. 1990;111:1465–76.PubMedView ArticleGoogle Scholar
- Beylkin DH, Allen DL, Leinwand LA. MyoD, Myf5, and the calcineurin pathway activate the developmental myosin heavy chain genes. Dev Biol. 2006;294:541–53.PubMedView ArticleGoogle Scholar
- Konig S, Burkman J, Fitzgerald J, Mitchell M, Su L, Stedman H. Modular organization of phylogenetically conserved domains controlling developmental regulation of the human skeletal myosin heavy chain gene family. J Biol Chem. 2002;277:27593–605.PubMedView ArticleGoogle Scholar
- Narusawa M, Fitzsimons RB, Izumo S, Nadal-Ginard B, Rubinstein NA, Kelly AM. Slow myosin in developing rat skeletal muscle. J Cell Biol. 1987;104:447–59.PubMedView ArticleGoogle Scholar
- Hughes SM, Cho M, Karsch-Mizrachi I, Travis M, Silberstein L, Leinwand LA, et al. Three slow myosin heavy chains sequentially expressed in developing mammalian skeletal muscle. Dev Biol. 1993;158:183–99.PubMedView ArticleGoogle Scholar
- Bormioli SP, Sartore S, Vitadello M, Schiaffino S. “Slow” myosins in vertebrate skeletal muscle. An immunofluorescence study. J Cell Biol. 1980;85:672–81.PubMedView ArticleGoogle Scholar
- Rossi AC, Mammucari C, Argentini C, Reggiani C, Schiaffino S. Two novel/ancient myosins in mammalian skeletal muscles: MYH14/7b and MYH15 are expressed in extraocular muscles and muscle spindles. J Physiol. 2010;588:353–64.PubMed CentralPubMedView ArticleGoogle Scholar
- Walro JM, Kucera J. Why adult mammalian intrafusal and extrafusal fibers contain different myosin heavy-chain isoforms. Trends Neurosci. 1999;22:180–4.PubMedView ArticleGoogle Scholar
- Rubinstein NA, Kelly AM. Development of muscle fiber specialization in the rat hindlimb. J Cell Biol. 1981;90:128–44.PubMedView ArticleGoogle Scholar
- Condon K, Silberstein L, Blau HM, Thompson WJ. Development of muscle fiber types in the prenatal rat hindlimb. Dev Biol. 1990;138:256–74.PubMedView ArticleGoogle Scholar
- Faerman A, Shani M. The expression of the regulatory myosin light chain 2 gene during mouse embryogenesis. Development. 1993;118:919–29.PubMedGoogle Scholar
- DeNardi C, Ausoni S, Moretti P, Gorza L, Velleca M, Buckingham M, et al. Type 2X-myosin heavy chain is coded by a muscle fiber type-specific and developmentally regulated gene. J Cell Biol. 1993;123:823–35.PubMedView ArticleGoogle Scholar
- Lu BD, Allen DL, Leinwand LA, Lyons GE. Spatial and temporal changes in myosin heavy chain gene expression in skeletal muscle development. Dev Biol. 1999;216:312–26.PubMedView ArticleGoogle Scholar
- Agbulut O, Noirez P, Beaumont F, Butler-Browne G. Myosin heavy chain isoforms in postnatal muscle development of mice. Biol Cell. 2003;95:399–406.PubMedView ArticleGoogle Scholar
- Schiaffino S, Gorza L, Pitton G, Saggin L, Ausoni S, Sartore S, et al. Embryonic and neonatal myosin heavy chain in denervated and paralyzed rat skeletal muscle. Dev Biol. 1988;127:1–11.PubMedView ArticleGoogle Scholar
- Allen DL, Leinwand LA. Postnatal myosin heavy chain isoform expression in normal mice and mice null for IIb or IId myosin heavy chains. Dev Biol. 2001;229:383–95.PubMedView ArticleGoogle Scholar
- Brown DM, Parr T, Brameld JM. Myosin heavy chain mRNA isoforms are expressed in two distinct cohorts during C2C12 myogenesis. J Muscle Res Cell Motil. 2012;32:383–90.PubMedView ArticleGoogle Scholar
- LaFramboise WA, Guthrie RD, Scalise D, Elborne V, Bombach KL, Armanious CS, et al. Effect of muscle origin and phenotype on satellite cell muscle-specific gene expression. J Mol Cell Cardiol. 2003;35:1307–18.PubMedView ArticleGoogle Scholar
- Zhu H, Park S, Scheffler JM, Kuang S, Grant AL, Gerrard DE. Porcine satellite cells are restricted to a phenotype resembling their muscle origin. J Anim Sci. 2013;91:4684–91.PubMedView ArticleGoogle Scholar
- Kang LH, Rughani A, Walker ML, Bestak R, Hoh JF. Expression of masticatory-specific isoforms of myosin heavy-chain, myosin-binding protein-C and tropomyosin in muscle fibers and satellite cell cultures of cat masticatory muscle. J Histochem Cytochem. 2010;58:623–34.PubMed CentralPubMedView ArticleGoogle Scholar
- Butler-Browne GS, Herlicoviez D, Whalen RG. Effects of hypothyroidism on myosin isozyme transitions in developing rat muscle. FEBS Lett. 1984;166:71–5.PubMedView ArticleGoogle Scholar
- Gambke B, Lyons GE, Haselgrove J, Kelly AM, Rubinstein NA. Thyroidal and neural control of myosin transitions during development of rat fast and slow muscles. FEBS Lett. 1983;156:335–9.PubMedView ArticleGoogle Scholar
- Russell SD, Cambon N, Nadal-Ginard B, Whalen RG. Thyroid hormone induces a nerve-independent precocious expression of fast myosin heavy chain mRNA in rat hindlimb skeletal muscle. J Biol Chem. 1988;263:6370–4.PubMedGoogle Scholar
- Butler-Browne GS, Bugaisky LB, Cuenoud S, Schwartz K, Whalen RG. Denervation of newborn rat muscle does not block the appearance of adult fast myosin heavy chain. Nature. 1982;299:830–3.PubMedView ArticleGoogle Scholar
- Pandorf CE, Jiang W, Qin AX, Bodell PW, Baldwin KM, Haddad F. Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2012;302:R854–67.PubMed CentralPubMedView ArticleGoogle Scholar
- Sakakibara I, Santolini M, Ferry A, Hakim V, Maire P. Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype. PLoS Genet. 2014;10:e1004386.PubMed CentralPubMedView ArticleGoogle Scholar
- Fidzianska A. Human ontogenesis. I. Ultrastructural characteristics of developing human muscle. J Neuropathol Exp Neurol. 1980;39:476–86.PubMedView ArticleGoogle Scholar
- Barbet JP, Thornell LE, Butler-Browne GS. Immunocytochemical characterisation of two generations of fibers during the development of the human quadriceps muscle. Mech Dev. 1991;35:3–11.PubMedView ArticleGoogle Scholar
- Draeger A, Weeds AG, Fitzsimons RB. Primary, secondary and tertiary myotubes in developing skeletal muscle: a new approach to the analysis of human myogenesis. J Neurol Sci. 1987;81:19–43.PubMedView ArticleGoogle Scholar
- Cho M, Webster SG, Blau HM. Evidence for myoblast-extrinsic regulation of slow myosin heavy chain expression during muscle fiber formation in embryonic development. J Cell Biol. 1993;121:795–810.PubMedView ArticleGoogle Scholar
- Racca AW, Beck AE, Rao VS, Flint GV, Lundy SD, Born DE, et al. Contractility and kinetics of human fetal and human adult skeletal muscle. J Physiol. 2013;591:3049–61.PubMed CentralPubMedView ArticleGoogle Scholar
- Ecob-Prince M, Hill M, Brown W. Immunocytochemical demonstration of myosin heavy chain expression in human muscle. J Neurol Sci. 1989;91:71–8.PubMedView ArticleGoogle Scholar
- Smerdu V. Expression of myosin heavy chain transcripts within distinct types of human muscle fibres. Slovenia: University of Ljubljana; 2002.Google Scholar
- Butler-Browne GS, Barbet JP, Thornell LE. Myosin heavy and light chain expression during human skeletal muscle development and precocious muscle maturation induced by thyroid hormone. Anat Embryol (Berl). 1990;181:513–22.View ArticleGoogle Scholar
- Hailstones DL, Gunning PW. Characterization of human myosin light chains 1sa and 3nm: implications for isoform evolution and function. Mol Cell Biol. 1990;10:1095–104.PubMed CentralPubMedGoogle Scholar
- Sartore S, Mascarello F, Rowlerson A, Gorza L, Ausoni S, Vianello M, et al. Fibre types in extraocular muscles: a new myosin isoform in the fast fibres. J Muscle Res Cell Motil. 1987;8:161–72.PubMedView ArticleGoogle Scholar
- Wieczorek DF, Periasamy M, Butler-Browne GS, Whalen RG, Nadal-Ginard B. Co-expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature. J Cell Biol. 1985;101:618–29.PubMedView ArticleGoogle Scholar
- Eriksson PO, Butler-Browne GS, Thornell LE. Immunohistochemical characterization of human masseter muscle spindles. Muscle Nerve. 1994;17:31–41.PubMedView ArticleGoogle Scholar
- Rowlerson A, Gorza L, Schiaffino S. Immunohistochemical identification of spindle fiber types in mammalian muscle using type-specific antibodies to isoforms of myosin. In: The Muscle Spindle. London: Macmillan; 1985.Google Scholar
- Butler-Browne GS, Eriksson PO, Laurent C, Thornell LE. Adult human masseter muscle fibers express myosin isozymes characteristic of development. Muscle Nerve. 1988;11:610–20.PubMedView ArticleGoogle Scholar
- d’Albis A, Janmot C, Bechet JJ. Comparison of myosins from the masseter muscle of adult rat, mouse and guinea-pig. Persistence of neonatal-type isoforms in the murine muscle. Eur J Biochem. 1986;156:291–6.PubMedView ArticleGoogle Scholar
- Stal P, Eriksson PO, Schiaffino S, Butler-Browne GS, Thornell LE. Differences in myosin composition between human oro-facial, masticatory and limb muscles: enzyme-, immunohisto- and biochemical studies. J Muscle Res Cell Motil. 1994;15:517–34.PubMedView ArticleGoogle Scholar
- Toniolo L, Maccatrozzo L, Patruno M, Caliaro F, Mascarello F, Reggiani C. Expression of eight distinct MHC isoforms in bovine striated muscles: evidence for MHC-2B presence only in extraocular muscles. J Exp Biol. 2005;208:4243–53.PubMedView ArticleGoogle Scholar
- Reiser PJ, Bicer S, Chen Q, Zhu L, Quan N. Masticatory (;superfast’) myosin heavy chain and embryonic/atrial myosin light chain 1 in rodent jaw-closing muscles. J Exp Biol. 2009;212:2511–9.PubMedView ArticleGoogle Scholar
- Reiser PJ, Bicer S, Patel R, An Y, Chen Q, Quan N. The myosin light chain 1 isoform associated with masticatory myosin heavy chain in mammals and reptiles is embryonic/atrial MLC1. J Exp Biol. 2010;213:1633–42.PubMedView ArticleGoogle Scholar
- Murgia M, Nagaraj N, Deshmukh AS, Zeiler M, Cancellara P, Moretti I, et al. Single muscle fiber proteomics reveals unexpected mitochondrial specialization. EMBO Rep. 2015;16(3):387–95.PubMed CentralPubMedView ArticleGoogle Scholar
- Racca AW, Beck AE, McMillin MJ, Korte FS, Bamshad MJ, Regnier M. The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle. Hum Mol Genet. 2015;24(12):3348–58.PubMedView ArticleGoogle Scholar
- Zhou Y, Liu D, Kaminski HJ. Myosin heavy chain expression in mouse extraocular muscle: more complex than expected. Invest Ophthalmol Vis Sci. 2010;51:6355–63.PubMed CentralPubMedView ArticleGoogle Scholar
- Izumo S, Nadal-Ginard B, Mahdavi V. All members of the MHC multigene family respond to thyroid hormone in a highly tissue-specific manner. Science. 1986;231:597–600.PubMedView ArticleGoogle Scholar
- Ciciliot S, Schiaffino S. Regeneration of mammalian skeletal muscle. Basic mechanisms and clinical implications. Curr Pharm Des. 2010;16:906–14.PubMedView ArticleGoogle Scholar
- Esser K, Gunning P, Hardeman E. Nerve-dependent and -independent patterns of mRNA expression in regenerating skeletal muscle. Dev Biol. 1993;159:173–83.PubMedView ArticleGoogle Scholar
- Saggin L, Gorza L, Ausoni S, Schiaffino S. Cardiac troponin T in developing, regenerating and denervated rat skeletal muscle. Development. 1990;110:547–54.PubMedGoogle Scholar
- Carraro U, Dalla Libera L, Catani C. Myosin light and heavy chains in muscle regenerating in absence of the nerve: transient appearance of the embryonic light chain. Exp Neurol. 1983;79:106–17.PubMedView ArticleGoogle Scholar
- d’Albis A, Couteaux R, Janmot C, Roulet A, Mira JC. Regeneration after cardiotoxin injury of innervated and denervated slow and fast muscles of mammals. Myosin isoform analysis. Eur J Biochem. 1988;174:103–10.PubMedView ArticleGoogle Scholar
- Whalen RG, Harris JB, Butler-Browne GS, Sesodia S. Expression of myosin isoforms during notexin-induced regeneration of rat soleus muscles. Dev Biol. 1990;141:24–40.PubMedView ArticleGoogle Scholar
- Carraro U, Morale D, Mussini I, Lucke S, Cantini M, Betto R, et al. Chronic denervation of rat hemidiaphragm: maintenance of fiber heterogeneity with associated increasing uniformity of myosin isoforms. J Cell Biol. 1985;100:161–74.PubMedView ArticleGoogle Scholar
- Maier A, Gorza L, Schiaffino S, Pette D. A combined histochemical and immunohistochemical study on the dynamics of fast-to-slow fiber transformation in chronically stimulated rabbit muscle. Cell Tissue Res. 1988;254:59–68.PubMedView ArticleGoogle Scholar
- DiMario JX, Uzman A, Strohman RC. Fiber regeneration is not persistent in dystrophic (MDX) mouse skeletal muscle. Dev Biol. 1991;148:314–21.PubMedView ArticleGoogle Scholar
- Schiaffino S, Gorza L, Dones I, Cornelio F, Sartore S. Fetal myosin immunoreactivity in human dystrophic muscle. Muscle Nerve. 1986;9:51–8.PubMedView ArticleGoogle Scholar
- Eusebi V, Rilke F, Ceccarelli C, Fedeli F, Schiaffino S, Bussolati G. Fetal heavy chain skeletal myosin. An oncofetal antigen expressed by rhabdomyosarcoma. Am J Surg Pathol. 1986;10:680–6.PubMedView ArticleGoogle Scholar
- Schiaffino S, Gorza L, Sartore S, Saggin L, Carli M. Embryonic myosin heavy chain as a differentiation marker of developing human skeletal muscle and rhabdomyosarcoma. A monoclonal antibody study. Exp Cell Res. 1986;163:211–20.PubMedView ArticleGoogle Scholar
- Jerkovic R, Argentini C, Serrano-Sanchez A, Cordonnier C, Schiaffino S. Early myosin switching induced by nerve activity in regenerating slow skeletal muscle. Cell Struct Funct. 1997;22:147–53.PubMedView ArticleGoogle Scholar
- Kalhovde JM, Jerkovic R, Sefland I, Cordonnier C, Calabria E, Schiaffino S, et al. “Fast” and “slow” muscle fibres in hindlimb muscles of adult rats regenerate from intrinsically different satellite cells. J Physiol. 2005;562:847–57.PubMed CentralPubMedView ArticleGoogle Scholar
- Tajsharghi H, Oldfors A. Myosinopathies: pathology and mechanisms. Acta Neuropathol. 2013;125:3–18.PubMed CentralPubMedView ArticleGoogle Scholar
- Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ. Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat Genet. 2006;38:561–5.PubMedView ArticleGoogle Scholar
- Beck AE, McMillin MJ, Gildersleeve HI, Shively KM, Tang A, Bamshad MJ. Genotype-phenotype relationships in Freeman-Sheldon syndrome. Am J Med Genet A. 2014;164A:2808–13.PubMedView ArticleGoogle Scholar
- Beck AE, McMillin MJ, Gildersleeve HI, Kezele PR, Shively KM, Carey JC, et al. Spectrum of mutations that cause distal arthrogryposis types 1 and 2B. Am J Med Genet A. 2013;161A:550–5.PubMedView ArticleGoogle Scholar
- Toydemir RM, Chen H, Proud VK, Martin R, van Bokhoven H, Hamel BC, et al. Trismus-pseudocamptodactyly syndrome is caused by recurrent mutation of MYH8. Am J Med Genet A. 2006;140:2387–93.PubMedView ArticleGoogle Scholar
- Veugelers M, Bressan M, McDermott DA, Weremowicz S, Morton CC, Mabry CC, et al. Mutation of perinatal myosin heavy chain associated with a Carney complex variant. N Engl J Med. 2004;351:460–9.PubMedView ArticleGoogle Scholar
- Stratakis CA, Bertherat J, Carney JA. Mutation of perinatal myosin heavy chain. N Engl J Med. 2004;351:2556–8. author reply −8.PubMedView ArticleGoogle Scholar
- Drachman DB, Sokoloff L. The role of movement in embryonic joint development. Dev Biol. 1966;14:401–20.View ArticleGoogle Scholar
- Murray PD, Drachman DB. The role of movement in the development of joints and related structures: the head and neck in the chick embryo. J Embryol Exp Morphol. 1969;22:349–71.PubMedGoogle Scholar
- Velazquez CV, Walklate J, Deacon J, Geeves MA, Leinwand LA. Functional analysis of Freeman-Sheldon syndrome causing mutations on embryonic myosin. Biophys J. 2015;108:304a.View ArticleGoogle Scholar
- Buller AJ, Eccles JC, Eccles RM. Differentiation of fast and slow muscles in the cat hind limb. J Physiol. 1960;150:399–416.PubMed CentralPubMedView ArticleGoogle Scholar
- Buller AJ, Lewis DM. Further observations on the differentiation of skeletal muscles in the kitten hind limb. J Physiol. 1965;176:355–70.PubMed CentralPubMedView ArticleGoogle Scholar
- Close R. Dynamic properties of fast and slow skeletal muscles of the rat during development. J Physiol. 1964;173:74–95.PubMed CentralPubMedView ArticleGoogle Scholar
- Drachman DB, Johnston DM. Development of a mammalian fast muscle: dynamic and biochemical properties correlated. J Physiol. 1973;234:29–42.PubMed CentralPubMedView ArticleGoogle Scholar
- Close RI. Dynamic properties of mammalian skeletal muscles. Physiol Rev. 1972;52:129–97.PubMedGoogle Scholar
- Schiaffino S, Reggiani C. Molecular diversity of myofibrillar proteins: gene regulation and functional significance. Physiol Rev. 1996;76:371–423.PubMedGoogle Scholar
- Luff AR, Atwood HL. Changes in the sarcoplasmic reticulum and transverse tubular system of fast and slow skeletal muscles of the mouse during postnatal development. J Cell Biol. 1971;51:369–83.PubMed CentralPubMedView ArticleGoogle Scholar
- Reiser PJ, Moss RL, Giulian GG, Greaser ML. Shortening velocity and myosin heavy chains of developing rabbit muscle fibers. J Biol Chem. 1985;260:14403–5.PubMedGoogle Scholar
- Geiger PC, Bailey JP, Mantilla CB, Zhan WZ, Sieck GC. Mechanisms underlying myosin heavy chain expression during development of the rat diaphragm muscle. J Appl Physiol (1985). 2006;101:1546–55.View ArticleGoogle Scholar
- Sieck GC, Prakash YS, Han YS, Fang YH, Geiger PC, Zhan WZ. Changes in actomyosin ATP consumption rate in rat diaphragm muscle fibers during postnatal development. J Appl Physiol (1985). 2003;94:1896–902.View ArticleGoogle Scholar
- Zhan WZ, Watchko JF, Prakash YS, Sieck GC. Isotonic contractile and fatigue properties of developing rat diaphragm muscle. J Appl Physiol (1985). 1998;84:1260–8.Google Scholar
- Resnicow DI, Deacon JC, Warrick HM, Spudich JA, Leinwand LA. Functional diversity among a family of human skeletal muscle myosin motors. Proc Natl Acad Sci U S A. 2010;107:1053–8.PubMed CentralPubMedView ArticleGoogle Scholar
- Pellegrino MA, Canepari M, Rossi R, D’Antona G, Reggiani C, Bottinelli R. Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles. J Physiol. 2003;546:677–89.PubMed CentralPubMedView ArticleGoogle Scholar
- White J, Barro MV, Makarenkova HP, Sanger JW, Sanger JM. Localization of sarcomeric proteins during myofibril assembly in cultured mouse primary skeletal myotubes. Anat Rec (Hoboken). 2014;297:1571–84.View ArticleGoogle Scholar
- Lyons GE, Schiaffino S, Sassoon D, Barton P, Buckingham M. Developmental regulation of myosin gene expression in mouse cardiac muscle. J Cell Biol. 1990;111:2427–36.PubMedView ArticleGoogle Scholar
- Brittain T. Molecular aspects of embryonic hemoglobin function. Mol Aspects Med. 2002;23:293–342.PubMedView ArticleGoogle Scholar
- Razeghi P, Essop MF, Huss JM, Abbasi S, Manga N, Taegtmeyer H. Hypoxia-induced switches of myosin heavy chain iso-gene expression in rat heart. Biochem Biophys Res Commun. 2003;303:1024–7.PubMedView ArticleGoogle Scholar
- Slot IG, Schols AM, Vosse BA, Kelders MC, Gosker HR. Hypoxia differentially regulates muscle oxidative fiber type and metabolism in a HIF-1alpha-dependent manner. Cell Signal. 2014;26:1837–45.PubMedView ArticleGoogle Scholar
- Schiaffino S, Gorza L, Ausoni S. Troponin isoform switching in the developing heart and its functional consequences. Trends Cardiovasc Med. 1993;3:12–7.PubMedView ArticleGoogle Scholar
- Caplan AI, Fiszman MY, Eppenberger HM. Molecular and cell isoforms during development. Science. 1983;221:921–7.PubMedView ArticleGoogle Scholar
- Spudich JA. Hypertrophic and dilated cardiomyopathy: four decades of basic research on muscle lead to potential therapeutic approaches to these devastating genetic diseases. Biophys J. 2014;106:1236–49.PubMed CentralPubMedView ArticleGoogle Scholar
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