19-P020 Schmidtea mediterranea’s matrix metalloproteases and their importance for regeneration and survival

The most prominent and dramatic example of regeneration in vertebrates is the complete reconstitution of amphibian limbs and fish fins by epimorphic regeneration. Research into the molecular regulation of this fascinating biological problem is of high medical interest due to the potential application in replacing old or damaged tissues in humans. Retinoic acid (RA), a small lipophilic molecule which is synthesized from dietary sources of vitamin A, plays important roles during embryonic development by modulating gene expression. It is well-known that treatment with RA during limband fin regeneration causes a number of striking morphological effects on the regenerate, but its functional involvement in vertebrate appendage regeneration has not been addressed. We have now provided first evidence for the requirement of RA signaling for fin regeneration. We could show that RA signaling pathway components as well as potential targets are strongly expressed after amputation in the regenerating caudal fin of zebrafish. Inhibition of RA signaling by using a competitive reversible inhibitor of RA synthesis (DEAB) blocks regeneration of the larval fin. Moreover, regeneration is also impaired in homozygous aldh1a2 (neckless) mutant larvae. To address the involvement of RA signaling in adult fin regeneration, we have generated a transgenic line which allows the temporally controlled degradation of endogenous RA. Most importantly, inhibition of RA signaling during adult fin regeneration blocks the regeneration process. Together, our findings demonstrate an essential role for RA signaling in vertebrate appendage regeneration.