Photo credit: phys.org
Researchers Discover Key Timing Factor in Killifish Tail Regeneration
When it comes to the remarkable ability to regenerate lost limbs and tissues, humans find themselves at a disadvantage. While spontaneous injuries like amputation or spinal cord damage in humans often lead to permanent loss, several animals, including the African killifish, can effectively regrow lost structures. A recent exploration by the Stowers Institute for Medical Research sheds light on a critical aspect of this regenerative process—specifically, the timing of cellular responses to injury.
A new study published in iScience on September 20, 2024, examines how African killifish manage to restore their tail fins after being injured. The research, led by Augusto Ortega Granillo, Ph.D., under the supervision of Stowers President and Chief Scientific Officer Alejandro Sánchez Alvarado, Ph.D., investigates the complex molecular and cellular mechanisms that enable successful regeneration.
The team’s analysis reveals that while the quantity and location of repair cells are foundational to regeneration, the duration of their engagement in the repair process is also crucial. “One of the major questions in regeneration is how organisms assess the extent of their injuries,” noted Sánchez Alvarado. “This study introduces a new variable into the regeneration narrative. Understanding how to adjust the speed and timing of regenerative responses could inform therapies aimed at enhancing tissue repair in humans.”
After an injury occurs in the killifish tail, the remaining tissue must quickly assess the damage incurred and rally an appropriate number of repair cells for the needed duration. The synchronization of damage recognition, cell recruitment, and timing forms the basis of successful regeneration.
“When an animal capable of regenerating limbs experiences a small injury, how does it manage to regenerate only the damaged section rather than a completely new limb?” posed Sánchez Alvarado. To explore this query, the researchers looked into various injury locations on the killifish tail fin.
They discovered that skin cells, both at the injury site and in adjacent, unaffected regions, initiate a genetic program that readies the entire organism for a repair response. At the injury site, skin cells maintained this activity, transiently adjusting their state to remodel the surrounding extracellular matrix, the structural support system for cells.
Ortega Granillo drew a parallel to a sponge, explaining that this matrix captures and conveys signals secreted by damaged tissue, which guide repair cells towards the site. Failure to accurately interpret these signals could lead to incomplete or malformed regeneration.
“We were able to pinpoint when and where the temporary cell states are active in the fin tissue, particularly at 24 hours after the injury,” Ortega Granillo remarked. “This understanding enabled us to execute genetic modifications to further decipher these cellular roles during regeneration.”
To test whether the different cellular states relay key information to the extracellular matrix during healing, the researchers utilized CRISPR-Cas9 gene editing. They focused on a gene responsible for modifying the extracellular matrix, which was activated at the onset of the regeneration process.
By impairing this gene’s function, the researchers evaluated its influence on cellular communication within the matrix during regeneration.
“The modified killifish were unable to gauge the amount of tissue loss accurately,” stated Ortega Granillo. “While they could regenerate, the speed of growth was significantly slower. This suggests that the cells in the skin communicate with the matrix to indicate the extent of loss and adjust the growth rate accordingly.”
Interestingly, regardless of whether the injury was minor or severe, the genetically altered fish demonstrated increased rates of tissue regeneration. This indicates a possibility that matrix-altering cell states might enhance regeneration. Fine-tuning these cellular states could provide a pathway for stimulating more effective regenerative responses.
From an evolutionary viewpoint, the research pursues understanding why some species exhibit superior regenerative abilities while others, such as humans, are limited. By distilling general principles from high-regeneration organisms, researchers hope to apply these findings toward advancing regenerative medicine for human applications.
“Our objective is to comprehend how to shape and grow tissues effectively,” concluded Ortega Granillo. “For individuals experiencing injuries or organ failures, advancements in regenerative therapies could restore vital functions that have been compromised.”
More information:
Augusto Ortega Granillo et al, Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration, iScience (2024). DOI: 10.1016/j.isci.2024.110737
Citation:
Scientists uncover a critical component that helps killifish regenerate their fins (2024, September 26) retrieved from Phys.org
Source
phys.org