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Preparation of Primary Myogenic Precursor Cell/Myoblast Cultures from Basal Vertebrate Lineages
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BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development
Jaeyoung Shin1, Shuichi Watanabe1, Soraya Hoelper1
1Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
Elife
|December 2, 2016
Summary
BRAF signaling is crucial for limb muscle development by inducing myoblast migration and activating PAX3. This discovery reveals a positive feedback loop essential for skeletal muscle precursor cell migration during embryogenesis.
Area of Science:
- Developmental Biology
- Cell Biology
- Molecular Biology
Background:
- Skeletal muscle precursor cell migration is vital for limb development.
- PAX3 and MET signaling pathways are known regulators of this process.
Purpose of the Study:
- To investigate the role of BRAF in limb skeletal muscle formation and myoblast migration.
- To elucidate the molecular mechanisms linking MET, BRAF, and PAX3 in muscle development.
Main Methods:
- Mouse embryogenesis model.
- Analysis of BRAF localization and interaction partners using mass spectrometry.
- Site-directed mutagenesis to study PAX3 phosphorylation.
- C2C12 myoblast migration assays.
Main Results:
- BRAF acts downstream of MET and induces myoblast migration.
- BRAF interacts with and phosphorylates PAX3 at specific sites.
- PAX3 phosphorylation by BRAF is essential for promoting myoblast migration.
- PAX3 upregulates MET gene transcription.
Conclusions:
- BRAF directly activates PAX3, enhancing its role in myoblast migration.
- MET signaling through BRAF creates a positive feedback loop with PAX3.
- This feedback loop is critical for maintaining PAX3 and MET activity for limb muscle precursor cell migration.
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