Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae.
Elife
; 102021 05 06.
Article
en En
| MEDLINE
| ID: mdl-33955353
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regeneración
/
Xenopus laevis
/
Transducción de Señal
/
Proteínas Hedgehog
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Regeneración de la Medula Espinal
/
Larva
/
Músculos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Elife
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido