A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis

The temporal switch from progenitor cell proliferation to differentiation is essential for effective adult tissue repair. We previously reported the critical role of Notch signaling in the proliferative expansion of myogenic progenitors in mammalian postnatal myogenesis. We now show that the onset o...

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Bibliographic Details
Published in:Cell stem cell 2008-01, Vol.2 (1), p.50-59
Main Authors: Brack, Andrew S, Conboy, Irina M, Conboy, Michael J, Shen, Jeanne, Rando, Thomas A
Format: Article
Language:English
Subjects:
Adult
Animals
Cell Differentiation
Cell Lineage - physiology
Cell Proliferation
Cricetinae
Glycogen Synthase Kinase 3 - physiology
Humans
Mice
Muscle Development
Myoblasts - cytology
Myoblasts - physiology
Receptors, Notch - physiology
Signal Transduction
Wnt Proteins - physiology
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Summary:The temporal switch from progenitor cell proliferation to differentiation is essential for effective adult tissue repair. We previously reported the critical role of Notch signaling in the proliferative expansion of myogenic progenitors in mammalian postnatal myogenesis. We now show that the onset of differentiation is due to a transition from Notch signaling to Wnt signaling in myogenic progenitors and is associated with an increased expression of Wnt in the tissue and an increased responsiveness of progenitors to Wnt. Crosstalk between these two pathways occurs via GSK3beta, which is maintained in an active form by Notch but is inhibited by Wnt in the canonical Wnt signaling cascade. These results demonstrate that the temporal balance between Notch and Wnt signaling orchestrates the precise progression of muscle precursor cells along the myogenic lineage pathway, through stages of proliferative expansion and then differentiation, during postnatal myogenesis.
ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2007.10.006