BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development

Jaeyoung Shin, Shuichi Watanabe, Soraya Hoelper, Marcus Krüger, Sawa Kostin, Jochen Pöling, Thomas Kubin, Thomas Braun

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. We found that a fraction of BRAF accumulates in the nucleus after activation and endosomal transport to a perinuclear position. Mass spectrometry based screening for potential interaction partners revealed that BRAF interacts and phosphorylates PAX3. Mutation of BRAF dependent phosphorylation sites in PAX3 impaired the ability of PAX3 to promote migration of C2C12 myoblasts indicating that BRAF directly activates PAX3. Since PAX3 stimulates transcription of the Met gene we propose that MET signaling via BRAF fuels a positive feedback loop, which maintains high levels of PAX3 and MET activity required for limb muscle precursor cell migration.

Original languageEnglish
Article numbere18351
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
StatePublished - 1 Dec 2016
Externally publishedYes

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