Brack Andrew S, Conboy Irina M, Conboy Michael J, Shen Jeanne, Rando Thomas A
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305-5235 USA.
Cell Stem Cell. 2008 Jan 10;2(1):50-9. doi: 10.1016/j.stem.2007.10.006.
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.
祖细胞从增殖向分化的时间转换对于有效的成体组织修复至关重要。我们之前报道了Notch信号通路在哺乳动物出生后肌生成过程中肌源性祖细胞增殖性扩张中的关键作用。我们现在表明，分化的开始是由于肌源性祖细胞中从Notch信号通路向Wnt信号通路的转变，并且与组织中Wnt表达增加以及祖细胞对Wnt的反应性增强有关。这两条信号通路之间的串扰通过GSK3β发生，GSK3β在Notch信号通路中保持活性形式，但在经典Wnt信号级联反应中被Wnt抑制。这些结果表明，在出生后肌生成过程中，Notch和Wnt信号通路之间的时间平衡协调了肌肉前体细胞沿着肌源性谱系途径的精确进程，该进程经过增殖性扩张阶段然后进入分化阶段。
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