A molecular mechanism enabling continuous embryonic muscle growth - a balance between proliferation and differentiation

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 1041-1053 ◽  
Author(s):  
H. Amthor ◽  
B. Christ ◽  
K. Patel
Keyword(s):  
Sonic Hedgehog ◽  
Muscle Growth ◽  
Terminal Differentiation ◽  
Intrinsic Property ◽  
Bone Morphogenetic Protein 4 ◽  
Down Regulation ◽  
Morphogenetic Protein ◽  
Proliferation And Differentiation ◽  
Embryonic Muscle ◽  
Myod Expression

Embryonic muscle growth requires a fine balance between proliferation and differentiation. In this study we have investigated how this balance is achieved during chick development. Removal of ectoderm from trunk somites results in the down-regulation of Pax-3 expression and cell division of myogenic precursors is halted. This initially leads to an up-regulation of MyoD expression and to a burst in terminal differentiation but further muscle growth is arrested. Locally applied bone morphogenetic protein-4 (BMP-4) to somites mimics the effect of the ectoderm and stimulates Pax-3 expression which eventually results in excessive muscle growth in somites. Surprisingly, BMP-4 up-regulates expression of noggin which encodes a BMP-4 antagonist. This suggests that the proliferation enhancing activity of BMP-4 can be limited via up-regulation of noggin and that myogenic cells differentiate, as an intrinsic property, when deprived of BMP-4 influence. In contrast to BMP-4, Sonic hedgehog (Shh) locally applied to somites arrests muscle growth by down-regulation of Pax-3 and immediate up-regulation of MyoD expression. Such premature muscle differentiation in somites at tongue and limb levels prevents myogenic migration and thus tongue and limb muscle are not formed. Therefore, precise limitation of differentiation, executed by proliferative and Pax-3 promoting signals, is indispensable for continuous embryonic muscle growth.

Cell heterogeneity upon myogenic differentiation: down-regulation of MyoD and Myf-5 generates ‘reserve cells’

1998 ◽  
Vol 111 (6) ◽  
pp. 769-779 ◽  
Author(s):  
N. Yoshida ◽  
S. Yoshida ◽  
K. Koishi ◽  
K. Masuda ◽  
Y. Nabeshima
Keyword(s):  
Cell Cycle ◽  
Myogenic Differentiation ◽  
Significant Proportion ◽  
Ectopic Expression ◽  
Terminal Differentiation ◽  
Growth Conditions ◽  
Down Regulation ◽  
Undifferentiated Cells ◽  
Myoblast Cells ◽  
Myod Expression

When a proliferating myoblast culture is induced to differentiate by deprivation of serum in the medium, a significant proportion of cells escape from terminal differentiation, while the rest of the cells differentiate. Using C2C12 mouse myoblast cells, this heterogeneity observed upon differentiation was investigated with an emphasis on the myogenic regulatory factors. The differentiating part of the cell population followed a series of well-described events, including expression of myogenin, p21(WAF1), and contractile proteins, permanent withdrawal from the cell cycle and cell fusion, whereas the rest of the cells did not initiate any of these events. Interestingly, the latter cells showed an undetectable or greatly reduced level of MyoD and Myf-5 expression, which had been originally expressed in the undifferentiated proliferating myoblasts. When these undifferentiated cells were isolated and returned to the growth conditions, they progressed through the cell cycle and regained MyoD expression. These cells demonstrated identical features with the original culture on the deprivation of serum. They produced both MyoD-positive differentiating and MyoD-negative undifferentiated populations once again. Thus the undifferentiated cells in the serum-deprived culture were designated ‘reserve cells’. Upon serum deprivation, MyoD expression rapidly decreased as a result of down-regulation in approximately 50% of the cells. After this heterogenization, MyoD positive cells expressed myogenin, which is the earliest known event of terminal differentiation and marks irreversible commitment to this, while MyoD-negative cells did not differentiate and became the reserve cells. We also demonstrated that ectopic expression of MyoD converted the reserve cells to differentiating cells, indicating that down-regulation of MyoD is a causal event in the formation of reserve cells.

scholarly journals Down-regulation of BMP8A, SMADs 1/5/8 and BAX Proteins Following Methotrexate-treatment in Testicular Tissue of Swiss Albino Mice

2021 ◽  
pp. 1-9
Author(s):  
Olajumoke Omolara Ojo ◽  
Oluwadamilare Oluwaseun Ajayi ◽  
Babafemi Tosin Ogunbiyi
Keyword(s):  
Sertoli Cells ◽  
Sperm Count ◽  
Testicular Tissue ◽  
Ultrastructural Changes ◽  
Down Regulation ◽  
Group I ◽  
Morphogenetic Protein ◽  
Proliferation And Differentiation ◽  
Albino Mice

Several studies on the adverse effects of methotrexate have been reported, especially its implication in the degeneration of spermatogenesis, reduced sperm count and ultimate male infertility. As an antagonist, methotrexate (MTX) uses folic acid to obstruct the production of some biomolecules involved in synthesis of DNA, RNA and protein. It is used in the treatment of cancer and other diseases such as psoriasis, and rheumatism. Reports have also revealed that the expression of Bone Morphogenetic Protein (BMP8a) promotes spermatogenesis and fertility through the induction and activation of signaling sets of transcription factors, SMAD1/5/8. Hence, the expressions of these proteins and role of apoptosis are crucial to understand the mechanism involved in Methotrexate-induced infertility. In view of this, albino mice (Swiss strain) were randomly sorted to four groups. Group I served as control while groups II, III & IV (n=5) were treated with 5, 10 and 20mg/kg/day of Methotrexate (IP) respectively. Expressions of BMP8A and SMADs 1/ 5/ 8 were done by PCR and Western blotting techniques. Germ cell apoptosis was measured by flow cytometry and immunohistochemistry techniques. Ultrastructural changes were assessed in leydig cells as well as sertoli cells. The results of this study reveal a down-regulation of BMP8A and SMAD1/5/8 proteins in a dose-dependent pattern. Induction of apoptosis was also confirmed by the expression of primary apoptotic Bax antibody. The sertoli cells which play their major roles of nourishing and protecting the development of sperm cells were severely impaired too. These findings suggest that the function of BMP8A and SMAD1/5/8 proteins in promoting proliferation and differentiation of spermatogonia was severely disrupted following methotrexate exposure. Caution should therefore be taken when administering this drug.

scholarly journals Follistatin Regulates Bone Morphogenetic Protein-7 (BMP-7) Activity to Stimulate Embryonic Muscle Growth

2002 ◽  
Vol 243 (1) ◽  
pp. 115-127 ◽  
Author(s):  
Helge Amthor ◽  
Bodo Christ ◽  
Fiza Rashid-Doubell ◽  
C.Fred Kemp ◽  
Emily Lang ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Muscle Growth ◽  
Bone Morphogenetic Protein 7 ◽  
Morphogenetic Protein ◽  
Embryonic Muscle

scholarly journals MyoD regulates apoptosis of myoblasts through microRNA-mediated down-regulation of Pax3

2010 ◽  
Vol 191 (2) ◽  
pp. 347-365 ◽  
Author(s):  
Hiroyuki Hirai ◽  
Mayank Verma ◽  
Shuichi Watanabe ◽  
Christopher Tastad ◽  
Yoko Asakura ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Untranslated Region ◽  
Terminal Differentiation ◽  
Wild Type ◽  
Down Regulation ◽  
Muscle Stem Cells ◽  
Myod Gene ◽  
Myod Expression

The molecules that regulate the apoptosis cascade are also involved in differentiation and syncytial fusion in skeletal muscle. MyoD is a myogenic transcription factor that plays essential roles in muscle differentiation. We noticed that MyoD−/− myoblasts display remarkable resistance to apoptosis by down-regulation of miR-1 (microRNA-1) and miR-206 and by up-regulation of Pax3. This resulted in transcriptional activation of antiapoptotic factors Bcl-2 and Bcl-xL. Forced MyoD expression induces up-regulation of miR-1 and miR-206 and down-regulation of Pax3, Bcl-2, and Bcl-xL along with increased apoptosis in MyoD−/− myoblasts. In contrast, MyoD gene knockdown increases cell survival of wild-type myoblasts. The 3′ untranslated region of Pax3 mRNA contains two conserved miR-1/miR-206–binding sites, which are required for targeting of these microRNAs (miRNAs). Therefore, these data suggest that MyoD not only regulates terminal differentiation but also apoptosis through miRNA-mediated down-regulation of Pax3. Finally, MyoD, miR-1, and miR-206 are all down-regulated in quiescent satellite cells, which may be required for maintenance of muscle stem cells.

scholarly journals Expression of the Shh/Bmp4 signaling pathway during the development of anorectal malformations in a male rat model of prenatal exposure to di(n-butyl) phthalate

2015 ◽  
Vol 4 (2) ◽  
pp. 241-247 ◽  
Author(s):  
En-Hui Li ◽  
Sheng-Jie Liang ◽  
Wen-Lan Sun ◽  
Dong-Liang Xu ◽  
Yan Hong ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Prenatal Exposure ◽  
Rat Model ◽  
Anorectal Malformations ◽  
Male Rat ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein ◽  
Butyl Phthalate

Sonic hedgehog (Shh)/bone morphogenetic protein 4 (Bmp4) is an androgen-regulated signaling pathway that has been shown to be crucial for embryonic development.

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