Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae
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 r...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/61804 |
| _version_ | 1811201521586536448 |
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| author | Andrew M Hamilton Olga A Balashova Laura N Borodinsky |
| author_facet | Andrew M Hamilton Olga A Balashova Laura N Borodinsky |
| author_sort | Andrew M Hamilton |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T02:21:54Z |
| format | Article |
| id | doaj.art-197da252c55048d5bf5744e07141ea3e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:21:54Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-197da252c55048d5bf5744e07141ea3e2022-12-22T03:52:05ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.61804Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvaeAndrew M Hamilton0Olga A Balashova1Laura N Borodinsky2https://orcid.org/0000-0003-2937-7023Department of Physiology & Membrane Biology Shriners Hospitals for Children Northern California, University of California, Sacramento, School of Medicine, Sacramento, United StatesDepartment of Physiology & Membrane Biology Shriners Hospitals for Children Northern California, University of California, Sacramento, School of Medicine, Sacramento, United StatesDepartment of Physiology & Membrane Biology Shriners Hospitals for Children Northern California, University of California, Sacramento, School of Medicine, Sacramento, United StatesInducing 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.https://elifesciences.org/articles/61804spinal cord injuryskeletal muscle regenerationPKAnon-canonical hedgehog signalingCREBGli transcriptional activity |
| spellingShingle | Andrew M Hamilton Olga A Balashova Laura N Borodinsky Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae eLife spinal cord injury skeletal muscle regeneration PKA non-canonical hedgehog signaling CREB Gli transcriptional activity |
| title | Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae |
| title_full | Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae |
| title_fullStr | Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae |
| title_full_unstemmed | Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae |
| title_short | Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae |
| title_sort | non canonical hedgehog signaling regulates spinal cord and muscle regeneration in xenopus laevis larvae |
| topic | spinal cord injury skeletal muscle regeneration PKA non-canonical hedgehog signaling CREB Gli transcriptional activity |
| url | https://elifesciences.org/articles/61804 |
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