How are regenerative cells recruited during zebrafish larval tail regeneration?

点击翻译按钮获取中文摘要

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 digit tip. Aquatic vertebrates on the other hand, are able to regenerate large portions of organs including limb, tail, spinal cord, retina and heart. When comparable damage occurs in mammals, tissue fails 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 reinitiation of developmental genes is important to rebuild 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 tissue damage triggers developmental genes is crucial to further our understanding how successful regeneration takes place. A second reason for poor mammalian regeneration may be a failure to recruit new cells to the site of injury in sufficient numbers to restore the missing tissue. When tissue is damaged in mammals, limited numbers of regenerative cells are attracted to the injury. Studies in aquatic species indicate that large numbers of regenerative cells can be recruited from a diverse array of sources. The identification of the mechanisms that recruit cells to contribute to regeneration in aquatic species may help to facilitate regeneration in mammals by allowing more regenerative cells to be attracted to the damaged site. 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. By studying this process, we have identified a crucial regenerative pathway (called the Hedgehog pathway) that recruits regenerative cells to the site of injury enabling the redevelopment of the tail. In the first part of this project we aim to determine precisely which cells are recruited to repair the damaged tail and what roles do they play during regeneration. In the second part of the project we aim to determine how Hedgehog signalling acts on these cells to initiate regeneration. The knowledge gained from our study will hopefully 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, including those that act in the Hedgehog pathway. 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.