Linking developmental cell types with their regenerative counterparts.

Regenerative biology is a scientific field that aims to understand the mechanisms and limitations of regenerative capacity in different organisms. Although mammals are able to heal wounds and regrow many tissues such as skin and muscle, the regeneration of complex structures is limited to the liver, kidney and the tip of a finger. Aquatic vertebrates on the other hand, are able to regenerate large portions of organs and appendages including the limb, tail, spinal cord, retina and heart. When comparable damage occurs in mammals, tissues fail to regrow and scarring occurs.

Organ regeneration in aquatic vertebrates requires many of the same genes that are deployed during the initial development of the organ. This indicates that the reactivation of developmental genes is an important step in rebuilding the organ. One possible explanation for the poor regenerative potential observed in mammals is that damage does not trigger these developmental genes.

These genes are present in mammals but are simply not reactivated. Thus, the elucidation of the mechanism by which developmental genes are reactivated to restore missing tissue is crucial to further our understanding how successful regeneration takes place.

Our project focuses of zebrafish as a model for regeneration. When a small portion from the end of the tail is removed, the fish regenerate the missing tissue after 3 to 4 days. This project will compare cell types present during tail development to those seen in regeneration.

We aim to find out how similar tail development is to tail regeneration at the single cell and single gene level. The knowledge gained from our study may one day help us to develop new clinical approaches to organ regeneration in humans. Many of the same genes that are active during zebrafish regeneration are found in humans.

This suggests that we may be able to activate the same pathways in humans to mobilise untapped sources of regenerative cells and improve our regenerative capabilities.