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SYMPOSIA: Managing the Embryo for Performance |
Department of Animal Sciences, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster 44691
2 Corresponding author: velleman.1{at}osu.edu
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONREFERENCES |
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Key Words: extracellular matrix • growth factor • hyperplasia • hypertrophy • muscle fiber
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONREFERENCES |
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Muscle cell proliferation, migration, adhesion, and fusion are processes involved with the formation of multi-nucleated myotubes that will further differentiate into mature muscle fibers (Swartz et al., 1994). Not all muscle fibers form simultaneously during the prenatal period of muscle development. The first set of embryonic muscle fibers to form is termed primary fibers that have centrally located nuclei. Surrounding the primary fibers are mono-nucleated myogenic cells that will differentiate into secondary fibers. The secondary muscle fibers position is based on the location of the primary fibers. After the secondary fibers form, the Z band of the sarcomere, the contractile unit of muscle, will line up forming a mature muscle fiber.
Mechanisms of Muscle Growth
The process of muscle fiber formation is nearly complete at the time of hatch. Muscle growth can be separated into 2 periods, hyperplasia and hypertrophy. Hyperplasia refers to the embryonic increase in myoblast cell number. During the embryonic period of muscle development, myoblasts are proliferating, differentiating into multinucleated myotubes, and forming muscle fibers. After the prehatch formation of muscle fibers, fiber number is set at hatch (Smith, 1963). How the prehatch period of muscle growth affects posthatch muscle accretion has not received significant research attention to date.
For posthatch muscle growth to occur there must be an increase in protein synthesis, which is the direct consequence of more DNA resulting in increased transcription and translation. To acquire more DNA, there is a required increase in nuclei number. Because nuclei number derived from myoblasts is set at hatch, the new nuclei are derived from another cell type. Mauro (1961) identified the presence of a cell wedged between the plasma membrane and basement of skeletal muscle fibers. These cells were termed satellite cells because they have little cell cytoplasm. Mauro (1961) hypothesized that the satellite cells may be involved in postnatal muscle growth. Moss and LeBlond (1971) demonstrated that when 3H-thymidine was given to rats the label incorporated into the nuclei of the satellite cells for the first hour. After this time, the label was localized in the nuclei of the muscle fiber. Allen et al. (1979) reported that most of the nuclei in a mature muscle fiber are from satellite cells. After hatch, the satellite cells fuse with existing muscle fibers, causing an increase or hypertrophy in muscle fiber size.
Simply incorporating more satellite cell nuclei into a muscle fiber alone does not result in muscle hypertrophy. The balance between protein synthesis and degradation will modulate the hypertrophy process. To have an increase in muscle fiber size requires protein synthesis rates being higher than the rate of protein degradation. Degradation of muscle is largely regulated by the calpain system (Goll et al., 2003). The calpains, µ-calpain and m-calpain, are calcium-dependent proteases that do not degrade proteins to amino acids but disassemble the myofibril to the point of the Z-band. The further degradation of the myofibrillar structure is through the activity of the proteasome system. Calpastatin is a protein whose only known function is to inhibit the activity of the calpains.
Muscle Organization
Mature muscle fibers are surrounded and supported by 3 layers of connective tissue: endomysium, perimysium, and the epimysium. Connective tissue is composed of cells and an extracellular matrix. The extracellular matrix is composed of fibrous and nonfibrous proteins including collagens and proteoglycans. Muscle should contain well-defined muscle fibers as well as distinct endomysial spacing between the muscle fibers and well-defined perimysial spacing between the muscle fiber bundles. Maintaining this spacing is critical in preventing muscle fiber degeneration.
In broilers and turkeys selected for increased growth, it is common to observe more muscle fiber degeneration than in unimproved birds (Wilson et al., 1990; Dransfield and Sosnicki, 1999; Velleman et al., 2003). Figure 1
shows 16 wk posthatch breast muscle from a turkey randombred control line (RBC2) that is representative of a commercial 1967 turkey and 16 wk posthatch breast muscle from an F line turkey developed from the RBC2 line by selection for only increased 16-wk BW. The growth-selected F line has significant muscle fiber degeneration. In birds with increased muscle fiber degeneration, there is significantly reduced endomysial and perimysial spacing between the muscle fibers and the muscle fibers appear fragmented. The breast muscle is composed of glycolytic type II muscle fibers. The glycolytic mode of anaerobic respiration results in the formation of lactic acid. Lactic acid is largely removed from the muscle by the circulatory system to be converted into glycogen by the liver (Bangsbo et al., 1991). Velleman et al. (2003) observed in turkey breast muscles having increased muscle damage, there was a reduction in the capillary supply in the perimysial connective layer. A reduction in the blood supply to the muscle would increase lactic acid concentration and lead to muscle damage potentially associated with the pale, soft, and exudative condition. Turkey pale, soft, and exudative condition is associated with an increase in lactic acid and a decrease in pH (Sosnicki and Wilson, 1991).
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summarizes the effects of each of these growth factors on muscle cell function.
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Fibroblast growth factor 2 is a major growth factor involved in the regulation of muscle growth. It is a potent stimulator of myoblast and satellite cell proliferation and an intense inhibitor of differentiation (Dollenmeier et al., 1981). One biological effect of FGF2 during myogenesis is to inhibit the transcription of myogenin, a muscle specific transcriptional regulatory factor required for the initiation of myotube formation (Brunetti and Goldfine, 1990). By suppressing myogenin expression, FGF2 maintains the skeletal muscle cells in a state of proliferation. The turkey F line when compared with the RBC2 line that it was selected from has been shown to have higher FGF2 expression during satellite cell proliferation and embryonic stages of development (Liu et al., 2003). Increased FGF2 expression during the hyperplasia period of muscle growth would result in the formation of more muscle fibers prior to hatch. If more muscle fibers are present at time of hatch, this would provide more fiber availability for satellite cell fusion and muscle growth by hypertrophy. Fibroblast growth factor 2 is also a strong stimulator of satellite cell proliferation. The activation of satellite cell proliferation is critical in muscle hypertrophy. Feed-deprived turkey poults and chicks exhibit reduced satellite cell mitotic activity (Halevy et al., 2000; Mozdziak et al., 2002). The activity of the myoblasts and satellite cells is further influenced by the extrinsic or extracellular matrix environment surrounding the cells.
The extracellular matrix is composed of an organized network of proteins and polysaccharides, which are secreted by the muscle cells and localized in the connective layers surrounding the muscle fibers. The extracellular matrix consists mainly of collagens, proteoglycans, and glycoproteins like fibronectin. The extracellular matrix is a dynamic structure that changes in expression with the developmental age of the tissue and is cell type specific. The extracellular matrix communicates information back to the cell and regulates cellular gene expression. Certain extracellular matrix macromolecules, especially the proteoglycans, interact with growth factors and are required for the cell to elicit a response to the growth factor. Proteoglycans contain a central core protein with one or more attached carbohydrate residues called glycosaminoglycans. Glycosaminoglycans covalently attached to the core protein include chondroitin sulfate, keratan sulfate, dermatan sulfate, and heparan sulfate. Based on this definition, the proteoglycans are a diverse family of macromolecules that exhibit developmental and tissue specificity in terms of their expression.
In skeletal muscle, the proteoglycans play a major role in regulating myoblast and satellite cell responsiveness to the growth factors FGF2 and TGF-ß, and recent data suggest a role in myostatin responsiveness (Miura et al., 2006). The interaction of FGF2 with its high affinity receptor is mediated by the interaction of FGF2 with the heparan sulfate chains of heparan sulfate containing membrane-associated proteoglycans. Yayon et al. (1991) demonstrated that cells deficient in heparan sulfate proteoglycans and transfected to express the FGF2 receptor were unable to bind FGF2. The treatment of cells with chlorate to prevent glycosaminoglycan sulfation decreased the binding of FGF2 to its high affinity receptor (Olwin and Rapraeger, 1992). These studies have demonstrated that heparan sulfate functions as a low affinity coreceptor for FGF2. Because commercial poultry have been selected for enhanced muscling based on phenotype not by biological mechanisms involved in regulating muscle growth, it is not clear how growth selection has affected the expression of extracellular matrix macromolecules critical to the regulation of muscle growth during hyperplasia and hypertrophy.
To study how selection for growth and muscling has affected the expression of heparan sulfate proteoglycans during the embryonic and posthatch periods of development, research is in progress comparing the expression profiles of heparan sulfate proteoglycans in the RBC2 and F lines. During the embryonic and posthatch periods of age, heparan sulfate proteoglycan expression was higher in the growth selected F line compared with the unselected RBC2 line (Liu et al., 2002). The expression of FGF2 mRNA was higher earlier in embryonic development for the F line compared with the RBC2 line (Liu et al., 2003). This suggests that the growth-selected F line has the potential for increased FGF2 signaling, which would stimulate the proliferation of muscle cells leading to enhanced muscle development and growth. In a related study, McFarland et al. (2003) showed that fast growing turkey satellite cell populations were more responsive to FGF2, expressed more FGF2 mRNA, and had higher levels of heparan sulfate proteoglycans compared with slower growing satellite cell populations.
In muscle, 2 predominant groups of heparan sulfate proteoglycans expressed are the syndecans and glypicans. The syndecan family is composed of 4 members, syndecan-1 through -4, which have all been identified in skeletal muscle. The syndecans have a membrane spanning core protein possessing highly conserved cytoplasmic and transmembrane domains and a diverse ectodomain to which the glycosaminoglycan chains are attached (Carey, 1997; Rapraeger, 2001). Glypicans 1 through 6 have a core protein that contains conserved cysteine residues and glycosaminoglycan attachment sites. The glypicans are attached to the cell plasma membrane through a glycosylphosphatidylinositol anchor (David et al., 1990). Only glypican-1 has been reported in skeletal muscle. In vitro studies with C2C12 myoblasts have shown that syndecan-1, -3, and -4 expression are downregulated during skeletal muscle differentiation (Larraín et al., 1997; Fuentealba et al., 1999), whereas syn-decan-2 remained unchanged (Brandan and Larráin, 1998). In contrast, glypican-1 expression increased significantly during cell differentiation (Brandan et al., 1996). Syndecans and glypicans mediate FGF2 binding to fibro-blast growth factor receptors and regulated FGF2 activity (Steinfeld et al., 1996; Filla et al., 1998). The different expression patterns of syndecan-1 and glypican imply that these 2 proteoglycans may have functional differences in regulating cellular responsiveness to FGF2. To investigate the expression of syndecan-1 and glypican-1 as it relates to muscle development, studies have been ongoing in the author’s laboratory measuring the expression of syndecan-1 and glypican-1 in the F and RBC2 lines during embryonic and posthatch development (Liu et al., 2004, 2006).
Embryonic expression of syndecan-1 is higher at d 14 and 16 in the growth-selected F line compared with the RBC2 line. Glypican-1 expression is higher in the F line compared with the RBC2 line beginning at d 18. These results support the findings that syndecan-1 and glypican-1 are differentially expressed. Elevated syndecan-1 expression coincides with the period of muscle cell proliferation and is followed directly by high levels of glypican-1 expression. This expression profile of syndecan-1 and glypican-1 in the F line may lead to more myoblast proliferation and the formation of more muscle fibers by hyperplasia. With more muscle fibers present at hatch, the opportunity for muscle fiber growth by hypertrophy exists.
Implications for the Poultry Industry
In summary, a number of factors are involved in the molecular regulation of muscle growth. Developing a comprehensive understanding of the mechanisms of hyperplasia and hypertrophy is critical to the improvement and maintenance of poultry meat quality. The poultry industry has largely selected animals based on phenotypic growth rate and muscling and by using this approach has likely favored selection based on hypertrophy rather than hyperplasia. Hypertrophy will result in larger muscle fibers that have been observed in broiler breast meat (Dransfield and Sosnicki, 1999). In the case of skeletal muscle, this type of selection regimen will alter muscle fiber proportions (Dransfield and Sosnicki, 1999). As well as muscle fiber proportions being modified, the connective tissue spacing surrounding the muscle fibers will be changed resulting in a situation that could be detrimental to muscle health and subsequently meat quality.
The extracellular matrix macromolecules especially the proteoglycans will affect a number of properties critical to muscle growth and meat quality including water-holding capacity and growth factor regulation. The growth factor FGF2, for example, is a potent stimulator of muscle growth and a strong inhibitor of differentiation. For the muscle cells to elicit a response to FGF2, the FGF2 must bind to heparan sulfate containing proteoglycans. Selection for increased 16-wk BW in turkeys has been shown to increase FGF2 and heparan sulfate proteoglycan expression during the embryonic phase of growth (Liu et al., 2002, 2003). These changes in FGF2 and heparan sulfate proteoglycan expression would prolong the period of proliferation and likely result in muscle growth through hyperplasia. Perhaps the poultry industry should develop strategies to include screening for the expression of key genes related to muscle growth by hyperplasia and hypertrophy.
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FOOTNOTES |
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Received for publication August 7, 2006. Accepted for publication October 7, 2006.
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REFERENCES |
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