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  • 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.

eLife (2021-05-07)
Andrew M Hamilton, Olga A Balashova, Laura N Borodinsky
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cyclopamine hydrate, ≥98% (HPLC)
Sigma-Aldrich
Goat Anti-Mouse IgG Antibody, HRP conjugate, Upstate®, from goat
Sigma-Aldrich
Smoothened Agonist, SAG, A cell-permeable Smoothened Agonist, SAG, CAS 364590-63-6, modulates the coupling of Smo with its downstream effector by interacting with the Smo heptahelical domain (KD = 59 nM).
Sigma-Aldrich
Anti-phospho-Histone H3 (Ser10) Antibody, Mitosis Marker, Upstate®, from rabbit