Shh signaling directs dorsal ventral patterning in the regenerating X. tropicalis spinal cord

bioRxiv preprint, 2024 · DOI: https://doi.org/10.1101/2024.10.18.619160 · Published: October 19, 2024

Simple Explanation

Tissue development and regeneration rely on signals to organize cells. One key signal is Sonic Hedgehog (Shh), important for setting up the spinal cord's structure during development. This study looks at how Shh affects the spinal cord's organization during regeneration in Xenopus tropicalis tadpoles. Researchers found that certain cell markers are located in specific areas (dorsal, intermediate, ventral) and that these areas change when Shh signaling is messed with. The cells in the regenerating spinal cord are more sensitive to changes in Shh signaling than cells in uninjured tissue. This suggests that the way cells respond to developmental signals changes during regeneration.

Study Duration

4 days

Participants

NF stage 41 and 46 X. tropicalis tadpoles

Evidence Level

Not specified

Key Findings

1
Neural progenitor markers Msx1/2, Nkx6.1, and Nkx2.2 are confined to dorsal, intermediate and ventral spatial domains, respectively, in both the uninjured and regenerating spinal cord.
2
D/V domains are more sensitive to Shh perturbation during regeneration than uninjured tissue.
3
Shh signaling is necessary and sufficient for D/V NPC patterning during regeneration.

Research Summary

The study confirms that uninjured, regenerative stage Xenopus tropicalis tadpoles maintain expression of developmental markers of D/V NPC domains, and demonstrates that these domains are present during regeneration. D/V patterning is dependent on Shh signaling in similar manner to embryogenesis, with Shh activating expression of the intermediate and ventral domain transcription factors and inhibiting expression of dorsal markers. Regenerating cells show greater sensitivity to Shh perturbations than uninjured cells.

Practical Implications

Understanding Spinal Cord Regeneration

The findings contribute to a better understanding of the mechanisms that govern spinal cord regeneration, particularly the role of Shh signaling in D/V patterning.

Potential Therapeutic Targets

Identifying the specific signals and cellular responses involved in regeneration may lead to the development of therapeutic strategies to promote spinal cord repair after injury.

Comparative Regeneration Studies

The study highlights species-specific differences in Shh signaling during spinal cord regeneration, emphasizing the importance of comparative studies across different vertebrate species.

Study Limitations

1
The exact signal transduction mechanism of Shh as a morphogen in spinal cord regeneration requires further testing.
2
How the perturbation of NPC positional identity by Shh is propagated to post-mitotic neurons and ultimately to spinal cord function remains unclear.
3
The study focuses on early stages of regeneration (up to 4 dpa), and longer-term effects of Shh perturbation on spinal cord function were not investigated.

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