Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae.
Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae.
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DOI：
10.7554/elife.61804
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发表时间：
2021-05-06
期刊：
影响因子：
7.7
通讯作者：
Borodinsky LN
中科院分区：
文献类型：
--
作者：
Hamilton AM;Balashova OA;Borodinsky LN
诱导受损脊髓再生是现代医学面临的最大挑战之一。来自各种模式生物的研究表明，Hedgehog（Hh）信号可能是驱动再生的有用靶标。然而，Hh信号介导的组织再生的机制仍不清楚。在这里，我们研究了Hh信号在截肢后尾巴再生非洲爪蟾幼虫。我们发现，虽然Smoothened（Smo）的活动是必要的适当的脊髓和骨骼肌再生，转录活性的经典Hh效应Gli抑制截肢后立即，和抑制Gli 1/2的表达或转录活性对再生的影响最小。相反，我们证明，蛋白激酶A是必要的肌肉和脊髓的再生，在音乐会和独立的Smo，分别，其下游效应CREB激活脊髓截肢后，在一个Smo依赖的方式。我们的研究结果表明，Hh信号的非经典机制是必要的脊髓和肌肉再生。
Inducing regeneration in injured spinal cord represents one of modern medicine’s greatest challenges. Research from a variety of model organisms indicates that Hedgehog (Hh) signaling may be a useful target to drive regeneration. However, the mechanisms of Hh signaling-mediated tissue regeneration remain unclear. Here, we examined Hh signaling during post-amputation tail regeneration in Xenopus laevis larvae. We found that while Smoothened (Smo) activity is essential for proper spinal cord and skeletal muscle regeneration, transcriptional activity of the canonical Hh effector Gli is repressed immediately following amputation, and inhibition of Gli1/2 expression or transcriptional activity has minimal effects on regeneration. In contrast, we demonstrate that protein kinase A is necessary for regeneration of both muscle and spinal cord, in concert with and independent of Smo, respectively, and that its downstream effector CREB is activated in spinal cord following amputation in a Smo-dependent manner. Our findings indicate that non-canonical mechanisms of Hh signaling are necessary for spinal cord and muscle regeneration.