A temporal switch from Notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis
A temporal switch from Notch to Wnt signaling in muscle stem cells is necessary for normal adult myogenesis
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DOI：
10.1016/j.stem.2007.10.006
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发表时间：
2008-01-01
期刊：
影响因子：
23.9
通讯作者：
Rando, Thomas A.
中科院分区：
文献类型：
--
作者：
Brack, Andrew S.;Conboy, Irina M.;Rando, Thomas A.
从祖细胞增殖到分化的时间转换对于有效的成人组织修复是必不可少的。我们先前报道了Notch信号在哺乳动物出生后肌发生中肌源性祖细胞增殖扩张中的关键作用。我们现在表明，分化的开始是由于在肌源性祖细胞中从Notch信号传导到Wnt信号传导的转变，并且与组织中Wnt表达增加和祖细胞对Wnt的反应性增加相关。这两种途径之间的串扰通过GSK 3 β发生，GSK 3 β通过Notch保持活性形式，但在经典Wnt信号级联中被Wnt抑制。这些结果表明，Notch和Wnt信号传导之间的时间平衡协调肌肉前体细胞沿着肌源性谱系途径的精确进展，通过增殖扩张阶段，然后分化，在出生后肌发生。
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.