Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate
Molecular pathways needed for regeneration of spinal cord and muscle in a vertebrate
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DOI：
10.1016/s1534-5807(03)00233-8
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发表时间：
2003-09-01
影响因子：
11.8
通讯作者：
Slack, JMW
中科院分区：
文献类型：
--
作者：
Beck, CW;Christen, B;Slack, JMW
青蛙蝌蚪的尾巴，包括脊髓、肌肉和脊索，在部分切断后再生。我们表明，在非洲爪蟾，这发生在整个发展过程中，除了一个“不应期”之间的阶段45和47，当尾巴愈合没有再生。在此不应期期间，通过激活BMP或Notch信号传导途径可以实现再生。相反，再生可以通过抑制任一途径在后期再生阶段被阻止。BMP信号传导将引起所有组织的再生，而Notch信号传导激活脊髓和脊索的再生，但不激活肌肉。Msx1的活化形式可以促进再生，其方式与BMP信号传导相同。上位性实验表明，BMP信号是上游的Notch信号，但施加一个独立的肌肉再生的影响。结果表明，再生能力可以通过重新激活发育程序的特定组件的遗传修饰来实现。
The tail of the frog tadpole, comprising spinal cord, muscle, and notochord, regenerates following partial amputation. We show that, in Xenopus, this occurs throughout development, except for a "refractory period" between stages 45 and 47, when tails heal over without regeneration. Regeneration can be enabled during this refractory period by activation of either the BMP or Notch signaling pathways. Conversely, regeneration can be prevented during the later, regenerative, stages by inhibition of either pathway. BMP signaling will cause regeneration of all tissues, whereas Notch signaling activates regeneration of spinal cord and notochord, but not muscle. An activated form of Msx1 can promote regeneration in the same way as BMP signaling. Epistasis experiments suggest that BMP signaling is upstream of Notch signaling but exerts an independent effect on muscle regeneration. The results demonstrate that regenerative capability can be enabled by genetic modifications that reactivate specific components of the developmental program.