Journal
CELL STEM CELL
Volume 2, Issue 1, Pages 50-59Publisher
CELL PRESS
DOI: 10.1016/j.stem.2007.10.006
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Funding
- NIA NIH HHS [AG23806, AG05902, F32 AG005902, R01 AG023806] Funding Source: Medline
- NIH HHS [DP1 OD000392] Funding Source: Medline
- NINDS NIH HHS [NS36409, R01 NS036409] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS036409] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R37AG023806, F32AG005902, R01AG023806] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [DP1OD000392] Funding Source: NIH RePORTER
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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 GSK3 beta, 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.
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