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Xenopus laevis as a Model to Identify Translation Impairment
Published on: September 27, 2015
p38 MAP kinase regulates the expression of XMyf5 and affects distinct myogenic programs during Xenopus development
Aviad Keren1, Eyal Bengal, Dale Frank
1Department of Biochemistry, Rappaport Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel.
Abstract:
The p38 MAPK signaling pathway is essential for skeletal muscle differentiation in tissue culture models. We demonstrate a novel role for p38 MAPK in myogenesis during early Xenopus laevis development. Interfering with p38 MAPK causes distinct defects in myogenesis. The initial expression of Myf5 is selectively blocked, while expression of MyoD is unaffected. Expression of a subset of muscle structural genes is reduced. Convergent extension movements are prevented and segmentation of the paraxial mesoderm is delayed, probably due to the failure of cells to withdraw from the cell cycle. Myotubes are properly formed; however, at later stages, they begin to degenerate, and the boundaries between somites disappear. Significant apoptotic cell death occurs in most parts of the somites. The ventral body wall muscle derived from migratory progenitor cells of the ventral somite region is poorly formed. Our data indicate that the developmental defects caused by p38alpha-knockdown were mediated by the loss of XMyf5 expression. Thus, this study identifies a specific intracellular pathway in which p38 MAPK and Myf5 proteins regulate a distinct myogenic program.
Insights
The p38 MAPK pathway is crucial for early muscle development in Xenopus. Blocking this pathway disrupts Myf5 expression, leading to muscle defects and cell death.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Genetics
Background:
- The p38 mitogen-activated protein kinase (MAPK) signaling pathway is recognized for its role in skeletal muscle differentiation in cell culture.
- Its specific functions during early vertebrate development, particularly in myogenesis, remain less understood.
Purpose of the Study:
- To investigate the role of the p38 MAPK pathway in early myogenesis during Xenopus laevis development.
- To identify specific downstream targets and developmental processes regulated by p38 MAPK in this context.
Main Methods:
- p38 MAPK signaling was inhibited in early Xenopus embryos.
- Gene expression patterns (Myf5, MyoD, muscle structural genes) were analyzed.
- Embryonic development, cell cycle status, somite formation, and apoptosis were assessed.
- The impact of p38alpha knockdown on XMyf5 expression was specifically examined.
Main Results:
- Inhibition of p38 MAPK selectively blocked Myf5 expression but not MyoD.
- Expression of several muscle structural genes was reduced.
- Convergent extension movements were impaired, and paraxial mesoderm segmentation was delayed, linked to cell cycle exit failure.
- Myotubes initially formed but later degenerated, accompanied by somite boundary loss and widespread apoptosis.
- Development of ventral body wall muscle was severely affected.
- Developmental defects correlated with the loss of XMyf5 expression.
Conclusions:
- p38 MAPK plays a critical, novel role in early Xenopus myogenesis.
- The pathway regulates a distinct myogenic program through the control of XMyf5 expression.
- This study elucidates a specific intracellular pathway involving p38 MAPK and Myf5 in regulating muscle development.
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