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Signals in Spinal Cord Regeneration of Xenopus Tropicalis

Study reveals the role of Shh in spinal cord healing in frogs.

Andrea Elizabeth Wills, A. Angell Swearer, S. B. Perkowski

― 6 min read


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Regeneration is the process by which some animals can repair or replace lost body parts. This ability has fascinated scientists for a long time, especially when looking at how these animals grow new tissues. In vertebrates, such as frogs and fish, the spinal cord’s restoration depends on specific signals. Understanding how these signals work can reveal important information about tissue regeneration.

The Role of Signals in Spinal Cord Development

During the early stages of development, the spinal cord is formed with the help of certain signals. Two important signals are called bone morphogenetic protein (BMP) and Sonic hedgehog (Shh). These molecules help cells know where they are located, which is crucial for forming different types of nerve cells in the spinal cord.

BMP is found in the upper part, or dorsal side, of the spinal cord, while Shh is present in the lower part, or ventral side. Cells in the spinal cord use these signals to decide whether they should become upper or lower nerve cells. The balance between these signals helps organize the spinal cord correctly during development.

Regeneration and its Mechanisms

In animals that can regenerate, like certain types of frogs and fish, one might think that they would use the same signals to regrow lost spinal cord cells. Some evidence supports this idea, while other findings suggest a different approach. For example, if BMP or Shh is missing, regeneration does not occur properly in animals like zebrafish or newts. But how Shh affects the regrowth of nerve cells can differ among species.

In axolotls, a type of salamander known for its regenerative abilities, Shh helps to form new nerve cells during regeneration. However, these cells often take on the identity of the original cells they are replacing. This means that some factors from the spinal cord before injury still play a role in regeneration. In contrast, other animals, like certain lizards, do not use Shh the same way and regenerate differently.

Xenopus tadpoles are interesting because they can regenerate their spinal cord when they are young but lose this ability as they grow older. When a tadpole loses part of its tail, Shh is produced in the notochord-a flexible rod that runs along the back. This signal is needed for the full regrowth of the spinal cord and muscle. However, it is not entirely clear if Shh acts in the same way during regeneration as it does during development in all cases.

Research Goals

To investigate how spinal cord regeneration works in Xenopus tropicalis, a type of frog that shares many features with Xenopus laevis, researchers aimed to see if the spinal cord reorganizes itself in the same way it does during early development. They looked at how specific markers, which indicate different types of nerve cells, are expressed in both uninjured and regenerating Spinal Cords. It was important to also find out if Shh was necessary for this process. Another aspect of the study was to see if the identity of nerve cells in healthy tadpoles could change in response to Shh.

Observations on Spinal Cord Structure

In healthy, uninjured tadpoles, researchers found that nerve progenitor cells (NPCs) were organized into distinct areas that corresponded to their development: upper, middle, and lower regions. These areas were marked by specific proteins, indicating that the cells were correctly arranged according to their identities.

When looking at the regenerating spinal cord, they found that the same regions were formed again. After severing part of the tail, tadpoles showed that the NPCs were organized similarly to the original spinal cord. This observation indicated that regeneration was following a structured pattern, recovering the original organization of the spinal cord.

The Importance of Shh in Regeneration

After determining that the regions were present during regeneration, the researchers examined how Shh influenced this process. They introduced chemicals to either block or enhance Shh activity in tadpoles. When researchers blocked Shh signaling, the tadpoles showed an increased number of upper region cells and a decrease in both middle and lower region cells. In contrast, enhancing Shh signaling shifted more cells to the lower region.

These findings suggested that Shh is essential for restoring the correct spinal cord structure after injury. It appears that Shh influences not only the organization of nerve progenitor cells but also their identities during regeneration.

Sensitivity of Regenerating Cells to Shh

The study also noted that regenerating cells responded differently to changes in Shh compared to uninjured cells. In uninjured tadpoles, the cells showed some sensitivity to Shh changes. However, the regenerating cells were more responsive and underwent more significant changes when Shh levels were modified.

Researchers observed the sensitivity to Shh signaling decreased as time passed after the injury. This reduction in sensitivity might reflect the cells maturing and entering a different phase in their development.

Differences Between Species

The research also highlighted some interesting differences between species regarding how Shh functions in regeneration. While in many vertebrates, Shh acts through specific pathways to arrange the spinal cord's structure, in others, like the axolotl, these pathways may not be as important for growth.

In Xenopus tropicalis, researchers found that both the notochord and the floor plate, both structures that produce Shh, are regenerated during the healing process. This suggests that both could contribute to signaling needed for proper regeneration, unlike other species where only one structure may provide this signal.

Conclusion

The findings from this study on Xenopus tropicalis enhance our understanding of spinal cord regeneration. It shows that not only is Shh necessary for proper patterning of the spinal cord during regeneration, but that these cells are particularly sensitive to changes in Shh levels early after injury.

The results suggest that regenerative ability in Xenopus is related to the capacity of nerve progenitor cells to respond to signals like Shh, which may also have implications for understanding regenerative medicine in other species. Future research in this area will likely focus on how these signals operate in more detail and how they impact the final function of the regenerating spinal cord.

Original Source

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

Abstract: Tissue development and regeneration rely on the deployment of embryonic signals to drive progenitor activity and thus generate complex cell diversity and organization. One such signal is Sonic Hedgehog (Shh), which establishes the dorsal-ventral (D/V) axis of the spinal cord during embryogenesis. However, the existence of this D/V axis and its dependence on Shh signaling during regeneration varies by species. Here we investigate the function of Shh signaling in patterning the D/V axis during spinal cord regeneration in Xenopus tropicalis tadpoles. We find that 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. These domains are altered by perturbation of Shh signaling. Additionally, we find that these D/V domains are more sensitive to Shh perturbation during regeneration than uninjured tissue. The renewed sensitivity of these neural progenitor cells to Shh signals represents a regeneration specific response and raises questions about how responsiveness to developmental patterning cues is regulated in mature and regenerating tissues.

Authors: Andrea Elizabeth Wills, A. Angell Swearer, S. B. Perkowski

Last Update: 2024-10-19 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.10.18.619160

Source PDF: https://www.biorxiv.org/content/10.1101/2024.10.18.619160.full.pdf

Licence: https://creativecommons.org/licenses/by-nc/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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