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Elife 2021 May 06;10. doi: 10.7554/eLife.61804.
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Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae.

Hamilton AM , Balashova OA , Borodinsky LN .

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.

PubMed ID: 33955353
PMC ID: PMC8137141
Article link: Elife
Grant support: [+]

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: creb1 gli1 gli2 hpse sag shh smo sox2
GO keywords: smoothened signaling pathway [+]
Antibodies: Gli2 Ab3 H3f3a Ab9 Lmnb1 Ab6 P-CREB Ab1 Somite Ab3 Sox2 Ab6 sonic hedgehog Ab1

Article Images: [+] show captions
References [+] :
Akazawa, The upregulated expression of sonic hedgehog in motor neurons after rat facial nerve axotomy. 2004, Pubmed