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Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway.

Horsley V, Friday BB, Matteson S, Kegley KM, Gephart J, Pavlath GK - J. Cell Biol. (2001)

Bottom Line: The growth defect is intrinsic to muscle cells, since the lack of NFATC2 in primary muscle cultures results in reduced cell size and myonuclear number in myotubes.Taken together, these results implicate a novel role for NFATC2 in skeletal muscle growth.We demonstrate that during growth of multinucleated muscle cells, myoblasts initially fuse to form myotubes with a limited number of nuclei and that subsequent nuclear addition and increases in myotube size are controlled by a molecular pathway regulated by NFATC2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Emory University, Atlanta, Georgia 30322, USA.

ABSTRACT
The nuclear factor of activated T cells (NFAT) family of transcription factors regulates the development and differentiation of several tissue types. Here, we examine the role of NFATC2 in skeletal muscle by analyzing adult NFATC2(-/)- mice. These mice exhibit reduced muscle size due to a decrease in myofiber cross-sectional area, suggesting that growth is blunted. Muscle growth was examined during regeneration after injury, wherein NFATC2- myofibers form normally but display impaired growth. The growth defect is intrinsic to muscle cells, since the lack of NFATC2 in primary muscle cultures results in reduced cell size and myonuclear number in myotubes. Retroviral-mediated expression of NFATC2 in the mutant cells rescues this cellular phenotype. Myonuclear number is similarly decreased in NFATC2(-/)- mice. Taken together, these results implicate a novel role for NFATC2 in skeletal muscle growth. We demonstrate that during growth of multinucleated muscle cells, myoblasts initially fuse to form myotubes with a limited number of nuclei and that subsequent nuclear addition and increases in myotube size are controlled by a molecular pathway regulated by NFATC2.

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Myofiber CSA in other muscles is also reduced in NFATC2−/− mice. The CSA of individual myofibers was measured in TA and masseter muscles of wild-type and NFATC2−/− mice. Data are mean ± standard error; n = 5–8 for wild-type and n = 3 for NFATC2−/− (*P < 0.05).
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Figure 2: Myofiber CSA in other muscles is also reduced in NFATC2−/− mice. The CSA of individual myofibers was measured in TA and masseter muscles of wild-type and NFATC2−/− mice. Data are mean ± standard error; n = 5–8 for wild-type and n = 3 for NFATC2−/− (*P < 0.05).

Mentions: To determine if the reduced myofiber CSA in NFATC2−/− mice is specific to the soleus muscle or a generalized muscle phenomenon, we analyzed myofiber CSA of TA and masseter muscles. These muscles were chosen for analysis because they differ from the soleus in several properties. In contrast with the soleus muscle, which is composed mainly of type I and type IIA MyHC isoforms, the TA contains primarily type IIb, and the masseter contains predominantly type IIx MyHC (Eason et al. 2000). In addition, the masseter exhibits differences in myoblast populations compared with limb muscles (Pavlath et al. 1998). The myofiber CSA of the TA is decreased 25% in NFATC2−/− mice compared with wild-type (Fig. 2). A similar decrease is observed in the masseter (Fig. 2). These data suggest that NFATC2 has a general role in regulating myofiber growth.


Regulation of the growth of multinucleated muscle cells by an NFATC2-dependent pathway.

Horsley V, Friday BB, Matteson S, Kegley KM, Gephart J, Pavlath GK - J. Cell Biol. (2001)

Myofiber CSA in other muscles is also reduced in NFATC2−/− mice. The CSA of individual myofibers was measured in TA and masseter muscles of wild-type and NFATC2−/− mice. Data are mean ± standard error; n = 5–8 for wild-type and n = 3 for NFATC2−/− (*P < 0.05).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169453&req=5

Figure 2: Myofiber CSA in other muscles is also reduced in NFATC2−/− mice. The CSA of individual myofibers was measured in TA and masseter muscles of wild-type and NFATC2−/− mice. Data are mean ± standard error; n = 5–8 for wild-type and n = 3 for NFATC2−/− (*P < 0.05).
Mentions: To determine if the reduced myofiber CSA in NFATC2−/− mice is specific to the soleus muscle or a generalized muscle phenomenon, we analyzed myofiber CSA of TA and masseter muscles. These muscles were chosen for analysis because they differ from the soleus in several properties. In contrast with the soleus muscle, which is composed mainly of type I and type IIA MyHC isoforms, the TA contains primarily type IIb, and the masseter contains predominantly type IIx MyHC (Eason et al. 2000). In addition, the masseter exhibits differences in myoblast populations compared with limb muscles (Pavlath et al. 1998). The myofiber CSA of the TA is decreased 25% in NFATC2−/− mice compared with wild-type (Fig. 2). A similar decrease is observed in the masseter (Fig. 2). These data suggest that NFATC2 has a general role in regulating myofiber growth.

Bottom Line: The growth defect is intrinsic to muscle cells, since the lack of NFATC2 in primary muscle cultures results in reduced cell size and myonuclear number in myotubes.Taken together, these results implicate a novel role for NFATC2 in skeletal muscle growth.We demonstrate that during growth of multinucleated muscle cells, myoblasts initially fuse to form myotubes with a limited number of nuclei and that subsequent nuclear addition and increases in myotube size are controlled by a molecular pathway regulated by NFATC2.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Emory University, Atlanta, Georgia 30322, USA.

ABSTRACT
The nuclear factor of activated T cells (NFAT) family of transcription factors regulates the development and differentiation of several tissue types. Here, we examine the role of NFATC2 in skeletal muscle by analyzing adult NFATC2(-/)- mice. These mice exhibit reduced muscle size due to a decrease in myofiber cross-sectional area, suggesting that growth is blunted. Muscle growth was examined during regeneration after injury, wherein NFATC2- myofibers form normally but display impaired growth. The growth defect is intrinsic to muscle cells, since the lack of NFATC2 in primary muscle cultures results in reduced cell size and myonuclear number in myotubes. Retroviral-mediated expression of NFATC2 in the mutant cells rescues this cellular phenotype. Myonuclear number is similarly decreased in NFATC2(-/)- mice. Taken together, these results implicate a novel role for NFATC2 in skeletal muscle growth. We demonstrate that during growth of multinucleated muscle cells, myoblasts initially fuse to form myotubes with a limited number of nuclei and that subsequent nuclear addition and increases in myotube size are controlled by a molecular pathway regulated by NFATC2.

Show MeSH
Related in: MedlinePlus