Studies on the role of PTP1B During Tissue Regeneration

Zebrafish, unlike humans, have an outstanding ability to regenerate complex organs, such as hearts and appendages. However, the genetic factors important for this process remain largely unknown. In preliminary studies, we identified the protein tyrosine phosphatase (PTP1B) as a regulator of tissue regeneration. A morpholino (antisense oligonucleotide) designed against the PTP1B gene, specifically knocks out protein expression. By mediating the PTP1B function,  cardiomyocyte (CM) proliferation increased. However, the potential role for PTP1B during appendage regeneration has not been explored. The main goals of this research project are to characterize PTP1B function during adult caudal fin regeneration and to assess its expression profile in the regenerating heart. Here we report that morpholino mediated depletion of PTP1B activity appears to increase appendage regeneration. Commercially available antibodies directed against mouse PTP1B were used to confirm our findings by immunohistochemistry.  However, these antibodies appear to be non-cross reactive with the zebrafish ortholog. We believe PTP1B is a negative regulator of tissue regeneration. Further studies will help to elucidate its mechanism of action, and will strengthen it as a potential therapeutic target gene to augment regenerative deficiencies in humans.