Non-canonical Hedgehog signaling regulates spinal cord and muscle regeneration in Xenopus laevis larvae

eLife, 2021 · DOI: https://doi.org/10.7554/eLife.61804 · Published: May 6, 2021

Simple Explanation

This study investigates how the Hedgehog (Hh) signaling pathway affects spinal cord and muscle regeneration in Xenopus laevis larvae after tail amputation. The researchers found that while Smoothened (Smo) activity is crucial for spinal cord and muscle regeneration, the typical transcriptional activity of the Hh effector Gli is suppressed shortly after amputation. The study also demonstrates that protein kinase A (PKA) is necessary for the regeneration of both muscle and spinal cord, working with and independently of Smo, respectively.

Study Duration

Not specified

Participants

Xenopus laevis larvae

Evidence Level

Not specified

Key Findings

1
Smoothened (Smo) activity is essential for spinal cord and skeletal muscle regeneration in Xenopus laevis larvae.
2
Transcriptional activity of the canonical Hh effector Gli is repressed immediately following amputation.
3
Protein kinase A (PKA) is necessary for regeneration of both muscle and spinal cord.

Research Summary

The study demonstrates that Hh signaling is necessary for regeneration of muscle and spinal cord in Xenopus larvae. Hh-Smo signaling is particularly important for NSC proliferation with regards to spinal cord regeneration. Canonical, Gli-dependent Hh signaling is endogenously downregulated after tail amputation, suggesting that Hh-Smo is acting primarily through a Gli-independent pathway.

Practical Implications

Targeted Therapies

Selectively enhancing regeneration-specific, non-canonical Hh signaling in spinal cord and muscle during a critical period following injury might promote the repair and replenishment of functional tissues.

Drug Development

Findings could inform the development of novel therapeutic strategies for spinal cord injuries and muscle regeneration by targeting specific non-canonical Hh pathways.

Understanding Regeneration

Provides new insights into the mechanisms of tissue regeneration and the role of non-canonical Hh signaling.

Study Limitations

1
The exact mechanisms by which PKA modulates regeneration, however, remain unclear.
2
KT75720 has been shown to also inhibit other kinases in cell line and cell-free studies.
3
It remains to be determined whether Smo-dependent muscle regeneration is acting directly on muscle stem cells or indirectly through signals from the spinal cord.

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