Thesis defence Alexander James Hale

Alexander James Hale from the Den Hertog group will defend his thesis “New Players in Zebrafish Caudal Fin Regeneration: Differential Requirement for Protein-Tyrosine Phosphatases” on the 19th of October. In his thesis he studies the role of protein-tyrosine phosphatases during the regeneration of the zebrafish caudal fin. Hale will defend his thesis at Leiden University, where Jeroen den Hertog is appointed as professor.

Hale studied the regeneration of the caudal fin in zebrafish embryos during the past five years. Before he started his PhD he studied in England. His bachelor diploma he received from the University of Manchester and his master diploma from the Imperial College in London. Now that he has successfully completed his PhD he will search for a job in synthetic biology. Hale: “I would enjoy playing with the chemical structure of organisms, to help make better medicins in the future.”

Fin regeneration
Unlike humans, zebrafish are capable of regenerating various organs. The caudal fin, for example, grows back after amputation. By studying the regeneration process in fish, scientists hope to gain more insight in the mechanism behind it. In the future they might be able to influence this process in humans.

Protein-tyrosine phosphatases
The focus of Hale’s research was the role of protein-tyrosine phosphatases (PTPs) during the regeneration of the caudal fin. PTPs play an important role in basic cellular processes, such as proliferation, differentiation and cell-cell adhesion. After amputation of the caudal fin of the zebrafish hydrogen peroxide is produced, a chemical that can oxidize PTPs. The oxidation of PTPs after amputation of the fin was however not shown before. Hale’s research shows that out of the 33 PTPs that he found in the caudal fin, only 8 are oxidized by hydrogen peroxide after amputation. These PTPs might play a role in the regeneration of the fin.

Pten and Shp2 required for fin regeneration
Hale investigated the importance of two PTPs, Pten and Shp2, during fin regeneration. To this end he generated zebrafish that do not make these PTPs. These fish were not able to regenerate their caudal fin after amputation. In addition, Hale showed that fin regeneration returned to normal when he induced the expression of the missing PTP. This shows that Pten and Shp2 are required for regeneration of the caudal fin in zebrafish embryos.

Outgrowth of the caudal fin
In his thesis, Hale also shows that Pten and Shp2 are both important during a specific phase of fin regeneration. The regeneration process consists of three phases: first wound healing occurs at the site of the amputation. After that a blastema is formed. During the last phase, this blastema grows out to generate a new fin. In fish without Pten or Shp2, only the last phase, the outgrowth of the fin, did not take place.

Mechanism
In his research, Hale shows the importance of (oxidation of) PTPs during zebrafish fin regeneration. Based on his thesis, the function and molecular mechanism of individual PTPs during fin regeneration can be studied further, which will provide us with more insight in the mechanism behind the regeneration process. Hale: “With the results from our research we can get a better picture of the processes that play a role during the first steps of regeneration. In addition, scientists can use the combination of techniques that we used in our research to gain more insight in various other processes in which PTPs are involved.”