scholarly journals IGF-II transcription in skeletal myogenesis is controlled by mTOR and nutrients

2003 ◽  
Vol 163 (5) ◽  
pp. 931-936 ◽  
Author(s):  
Ebru Erbay ◽  
In-Hyun Park ◽  
Paul D. Nuzzi ◽  
Christopher J. Schoenherr ◽  
Jie Chen
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Kinase Activity ◽  
Regulatory Elements ◽  
Myoblast Differentiation ◽  
Akt Pathway ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Development ◽  
Primary Target ◽  
Insulin Like Growth Factors

Insulin-like growth factors (IGFs) are essential for skeletal muscle development, regeneration, and hypertrophy. Although autocrine actions of IGF-II are known to initiate myoblast differentiation, the regulatory elements and upstream signaling pathways for myogenic expression of IGF-II remain elusive. Here, we report the regulation of IGF-II transcription by mTOR, as well as by amino acid sufficiency, through the IGF-II promoter 3 and a downstream enhancer during C2C12 myoblast differentiation. Furthermore, we present evidence that IGF production, and not IGF signaling, is the primary target for mTOR's function in the initiation of differentiation. Moreover, myogenic signaling by mTOR is independent of its kinase activity and mediated by the PI3K–Akt pathway. Our findings represent the first identification of a signaling pathway that regulates IGF-II expression in myogenesis and implicate the mTOR–IGF axis as a molecular link between nutritional levels and skeletal muscle development.

scholarly journals Myoferlin Regulates Wnt/β-Catenin Signaling-Mediated Skeletal Muscle Development by Stabilizing Dishevelled-2 Against Autophagy

2019 ◽  
Vol 20 (20) ◽  
pp. 5130 ◽  
Author(s):  
Shunshun Han ◽  
Can Cui ◽  
Haorong He ◽  
Xiaoxu Shen ◽  
Yuqi Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Development ◽  
Skeletal Muscle Atrophy ◽  
Myoblast Differentiation ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Development ◽  
Muscle Tissues ◽  
Underlying Mechanisms ◽  
Canonical Wnt

Myoferlin (MyoF), which is a calcium/phospholipid-binding protein expressed in cardiac and muscle tissues, belongs to the ferlin family. While MyoF promotes myoblast differentiation, the underlying mechanisms remain poorly understood. Here, we found that MyoF not only promotes C2C12 myoblast differentiation, but also inhibits muscle atrophy and autophagy. In the present study, we found that myoblasts fail to develop into mature myotubes due to defective differentiation in the absence of MyoF. Meanwhile, MyoF regulates the expression of atrophy-related genes (Atrogin-1 and MuRF1) to rescue muscle atrophy. Furthermore, MyoF interacts with Dishevelled-2 (Dvl-2) to activate canonical Wnt signaling. MyoF facilitates Dvl-2 ubiquitination resistance by reducing LC3-labeled Dvl-2 levels and antagonizing the autophagy system. In conclusion, we found that MyoF plays an important role in myoblast differentiation during skeletal muscle atrophy. At the molecular level, MyoF protects Dvl-2 against autophagy-mediated degradation, thus promoting activation of the Wnt/β-catenin signaling pathway. Together, our findings suggest that MyoF, through stabilizing Dvl-2 and preventing autophagy, regulates Wnt/β-catenin signaling-mediated skeletal muscle development.

scholarly journals Study on the transcriptional regulatory mechanism of the MyoD1 gene in Guanling bovine

RSC Advances ◽  
2018 ◽  
Vol 8 (22) ◽  
pp. 12409-12419
Author(s):  
Di Zhou ◽  
Houqiang Xu ◽  
Wei Chen ◽  
Yuanyuan Wang ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Regulatory Mechanism ◽  
Early Stage ◽  
Myoblast Differentiation ◽  
Differentiation Process ◽  
Skeletal Muscle Development ◽  
Transcriptional Regulatory Mechanism ◽  
Transcriptional Regulatory

The MyoD1 gene plays a key role in regulating the myoblast differentiation process in the early stage of skeletal muscle development.

The Mef2c gene is a direct transcriptional target of myogenic bHLH and MEF2 proteins during skeletal muscle development

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4623-4633 ◽  
Author(s):  
Da-Zhi Wang ◽  
M. Renee Valdez ◽  
John McAnally ◽  
James Richardson ◽  
Eric N. Olson
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Transcription Factors ◽  
Binding Site ◽  
Control Region ◽  
Muscle Development ◽  
Regulatory Elements ◽  
Skeletal Muscle Development ◽  
Helix Loop Helix

Members of the MEF2 family of transcription factors are upregulated during skeletal muscle differentiation and cooperate with the MyoD family of myogenic basic helix-loop-helix (bHLH) transcription factors to control the expression of muscle-specific genes. To determine the mechanisms that regulate MEF2 gene expression during skeletal muscle development, we analyzed the mouse Mef2c gene for cis-regulatory elements that direct expression in the skeletal muscle lineage in vivo. We describe a skeletal muscle-specific control region for Mef2c that is sufficient to direct lacZ reporter gene expression in a pattern that recapitulates that of the endogenous Mef2c gene in skeletal muscle during pre- and postnatal development. This control region is a direct target for the binding of myogenic bHLH and MEF2 proteins. Mutagenesis of the Mef2c control region shows that a binding site for myogenic bHLH proteins is essential for expression at all stages of skeletal muscle development, whereas an adjacent MEF2 binding site is required for maintenance but not for initiation of Mef2c transcription. Our findings reveal the existence of a regulatory circuit between these two classes of transcription factors that induces, amplifies and maintains their expression during skeletal muscle development.

scholarly journals Overexpression of the Rybp Gene Inhibits Differentiation of Bovine Myoblasts into Myotubes

2018 ◽  
Vol 19 (7) ◽  
pp. 2082
Author(s):  
Xiaotong Su ◽  
Yanfang Zhao ◽  
Yaning Wang ◽  
Le Zhang ◽  
Linsen Zan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Molecular Breeding ◽  
Theoretical Foundation ◽  
Negative Control ◽  
Myoblast Differentiation ◽  
Rna Seq ◽  
Skeletal Muscle Development ◽  
Morphological Differences ◽  
Bovine Skeletal Muscle

RING1 and YY1 binding protein (Rybp) genes inhibit myogenesis in mice, but there are no reports on the effects of these genes in cattle. The aim of this study is to investigate the roles of the Rybp gene on bovine skeletal muscle development and myoblast differentiation. In the present study, the Rybp gene was overexpressed in bovine myoblasts via adenovirus. RNA-seq was performed to screen differentially expressed genes (DEGs). The results showed that overexpressing the Rybp gene inhibits the formation of myotubes. The morphological differences in myoblasts began on the second day and were very significant 6 days after adenovirus induction. A total of 1311 (707 upregulated and 604 downregulated) DEGs were screened using RNA-seq between myoblasts with added negative control adenoviruses (AD-NC) and Rybp adenoviruses (AD-Rybp) after 6 days of induction. Gene ontology (GO) and KEGG analysis revealed that the downregulated DEGs were mainly involved in biological functions related to muscle, and, of the 32 pathways, those associated with muscle development were significantly enriched for the identified DEGs. This study can not only provide a theoretical basis for the regulation of skeletal muscle development in cattle by exploring the roles of the Rybp gene in myoblast differentiation, but it can also lay a theoretical foundation for molecular breeding of beef cattle.

scholarly journals Transcriptome-wide N6-Methyladenosine Methylome Profiling Reveals m6A Regulation of Skeletal Myoblast Differentiation in Cattle (Bos taurus)

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinran Yang ◽  
Jianfang Wang ◽  
Xinhao Ma ◽  
Jiawei Du ◽  
Chugang Mei ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Bos Taurus ◽  
Myoblast Differentiation ◽  
Potential Candidate ◽  
Mammalian Skeletal Muscle ◽  
Mrna Levels ◽  
Skeletal Myogenesis ◽  
Skeletal Muscle Development ◽  
Differentially Methylated Genes

N6-methyladenosine (m6A) is the most prevalent methylation modification of eukaryotic mRNA, and it plays an important role in regulating gene expression. Previous studies have found that m6A methylation plays a role in mammalian skeletal muscle development. However, the effect of m6A on bovine skeletal myogenesis are still unclear. Here, we selected proliferating myoblasts (GM) and differentiated myotubes (on the 4th day of differentiation, DM) for m6A-seq and RNA-seq to explore the m6A methylation modification pattern during bovine skeletal myogenesis. m6A-seq analysis revealed that m6A methylation was an abundant modification of the mRNA in bovine myoblasts and myotubes. We scanned 5,691–8,094 m6A-modified transcripts, including 1,437 differentially methylated genes (DMGs). GO and KEGG analyses revealed that DMGs were primarily involved in transcriptional regulation and RNA metabolism, as well as insulin resistance and metabolic pathways related to muscle development. The combined analysis further identified 268 genes that had significant changes at both m6A and mRNA levels, suggesting that m6A modification may regulate myoblast differentiation by mediating the expression of these genes. Furthermore, we experimentally confirmed four genes related to myogenesis, including MYOZ2, TWIST1, KLF5 and MYOD1, with differential changes in both m6A and mRNA levels during bovine myoblast differentiation, indicating that they can be potential candidate targets for m6A regulation of skeletal myogenesis. Our results may provide new insight into molecular genetics and breeding of beef cattle, and provide a reference for investigating the mechanism of m6A regulating skeletal muscle development.

scholarly journals Longitudinal epi-transcriptome profiling reveals the crucial role of m6A in prenatal skeletal muscle development of pigs

2019 ◽  
Author(s):  
Xinxin Zhang ◽  
Yilong Yao ◽  
Jinghua Han ◽  
Yalan Yang ◽  
Yun Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Transcriptome Profiling ◽  
Rna Modification ◽  
C2c12 Myoblast ◽  
Skeletal Muscle Development ◽  
The Status ◽  
The Stability ◽  
Myoblast Cells ◽  
And Function

AbstractBackgroundN6-methyladenosine (m6A) is the most abundant RNA modification and essentially participates in the regulation of skeletal muscle development. However, the status and function of m6A methylation in prenatal myogenesis remains unclear now.ResultsIn our present study, we first demonstrate that chemical suppression of m6A and knockdown METTL14 significantly inhibit the differentiation and promote the proliferation of C2C12 myoblast cells. The mRNA expression of m6A reader protein IGF2BP1, which functions to promote the stability of target mRNA, continually decreases during the prenatal skeletal muscle development. Thereafter, profiling transcriptome-wide m6A for six developmental stage of prenatal skeletal muscle, which spanning two important waves of pig myogenesis, were performed using a refined MeRIP sequencing technology that is optimal for small-amount of RNA samples. Highly dynamic m6A methylomes across different development stages were then revealed, with majority of the affected genes enriched in pathways of skeletal muscle development. In association with the transcriptome-wide alterations, transcriptional regulatory factors (MyoD) and differentiated markers (MyHC, MYH1) of muscle development are simultaneously regulated with m6A and IGF2BP1. Knockdown of IGF2BP1 also suppresses myotube formation and promotes cell proliferation.ConclusionsThe present study clarifies the dynamics of RNA m6A methylation in the regulation of prenatal skeletal muscle development, providing a data baseline for future developmental as well as biomedical studies of m6A functions in muscle development and disease.

scholarly journals Male-Biased gga-miR-2954 Regulates Myoblast Proliferation and Differentiation of Chicken Embryos by Targeting YY1

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1325
Author(s):  
Xiuxue Dong ◽  
Yu Cheng ◽  
Lingyun Qiao ◽  
Xin Wang ◽  
Cuiping Zeng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Expression Profiles ◽  
Myoblast Differentiation ◽  
Mammalian Skeletal Muscle ◽  
Loss Of Function ◽  
Skeletal Muscle Development ◽  
Chicken Muscle ◽  
Proliferation And Differentiation ◽  
Myoblast Proliferation

Previous studies have shown that gga-miR-2954 was highly expressed in the gonads and other tissues of male chickens, including muscle tissue. Yin Yang1 (YY1), which has functions in mammalian skeletal muscle development, was predicted to be a target gene of gga-miR-2954. The purpose of this study was to investigate whether gga-miR-2954 plays a role in skeletal muscle development by targeting YY1, and evaluate its function in the sexual dimorphism development of chicken muscle. Here, all the temporal and spatial expression profiles in chicken embryonic muscles showed that gga-miR-2954 is highly expressed in males and mainly localized in cytoplasm. Gga-miR-2954 exhibited upregulated expression of in vitro myoblast differentiation stages. Next, through the overexpression and loss-of-function experiments performed in chicken primary myoblasts, we found that gga-miR-2954 inhibited myoblast proliferation but promoted differentiation. During myogenesis, gga-miR-2954 could suppress the expression of YY1, which promoted myoblast proliferation and inhibited the process of myoblast cell differentiation into multinucleated myotubes. Overall, these findings reveal a novel role of gga-miR-2954 in skeletal muscle development through its function of the myoblast proliferation and differentiation by suppressing the expression of YY1. Moreover, gga-miR-2954 may contribute to the sex difference in chicken muscle development.

scholarly journals Label-Free LC-MS/MS Proteomics Analyses Reveal Proteomic Changes Accompanying MSTN KO in C2C12 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Lamei Wang ◽  
Yu Huang ◽  
Xiaolong Wang ◽  
Yulin Chen
Keyword(s):  
Skeletal Muscle ◽  
Immune System ◽  
Energy Metabolism ◽  
Signaling Pathway ◽  
Muscle Development ◽  
C2c12 Cells ◽  
C2c12 Myoblast ◽  
Label Free ◽  
Skeletal Muscle Development ◽  
Mitochondrial Energy Metabolism

Analysis of the proteome of myostatin (MSTN) knockout (KO) mouse C2C12 cells has proven valuable to studies investigating the molecular mechanisms by which MSTN regulates skeletal muscle development. To identify new protein/pathway alterations and candidate biomarkers for skeletal muscle development, we compared proteomic profiles of MSTN KO C2C12 cells (KO) with corresponding wild-type cells (NC) using a label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. A total of 2637 proteins were identified and quantified in KO cells. Among these proteins, 77 proteins were significantly differentially expressed, 38 upregulated, and 39 downregulated, in MSTN KO C2C12 cells. These significantly altered proteins are involved in metabolic processes, developmental processes, immune system processes, and the regulation of other biological processes. Enrichment analysis was utilized to link these alterations to biological pathways, which are predominantly related to oxidative phosphorylation, protein digestion and absorption, mitochondrion localisation, antigen processing and presentation, the MAPK signaling pathway, the PPAR signaling pathway, the PI3K-Akt signaling pathway, and the JAK-STAT signaling pathway. Upregulation of several proteins, including epoxide hydrolase, tropomyosin 1, Cyb5a, HTRA1, Cox6a1, CD109, Synap29, and Ugt1a6, likely enhanced skeletal muscle development, the immune system, and energy metabolism. Collectively, our results present a comprehensive proteomics analysis of MSTN KO C2C12 myoblast cells; we hypothesize that MSTN KO could activate p38MAPK signaling pathway by CDC42, and we further deciphered the function of MSTN in the regulation of skeletal muscle development, immune processes, and mitochondrial energy metabolism.

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