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Notch2 Expressed by Myofibers Influences Muscle Mass and Fiber Types

ABSTRACT: Notch receptors play crucial roles in the cell-fate decisions of tissue stem cells during development and regeneration. Notch1-3 receptors are expressed by satellite cells and their progeny. Here we found that Notch2, but not Notch1 or Notch3, was expressed in fully differentiated myofibers. Using transgenic mice that expressed a muscle-specific active form of Notch2 (N2ICD-mTG), we found that Notch2 activation remarkably reduced muscle mass and strength with a shift toward slow fibers. Transcriptome analyses revealed that growth differentiation factor 11 (GDF11) was highly up-regulated in muscles of N2ICD-mTG mice, and crucially, N2ICD-induced muscle atrophy was rescued by siRNA-mediated reduction of GDF11 expression. These data suggest that Notch2 functions in muscle to regulate muscle mass, in part, through induction of GDF11 expression, and reveal a novel aspect of Notch signaling in a terminally differentiated adult tissue.

ORGANISM(S): Mus musculus

PROVIDER: GSE83929 | GEO | 2020/01/01

REPOSITORIES: GEO

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Notch1 and Notch2 signaling from distinct cellular sources exclusively but cooperatively regulate fetal myogenesis

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