Biology

Dr Prayag Murawala
Universit�¤t Dresden DFG-Center for Regenerative Therapies Dresden

Axolotl (Ambystoma mexicanum) limb regeneration shows the most extensive regeneration of vertebrate endochondral skeleton known to date. Due to the ability to regenerate entirely new segments of functional skeleton, the axolotl serves as a model to understand the stem/progenitor pools required for patterned skeletal regeneration. In other vertebrate models, the periskeleton, bone marrow and growth plate have been the focus of intensive investigation of stem cell pools. Here, through long-term genetic fate mapping we show that in Axolotl, periskeletal cells rebuild
callus as in other vertebrates, but these cells ultimately display limited renewal. Their contribution is largely limited to extension of the remaining segment. In contrast, extra-skeletal soft/loose connective tissue cells build the vast majority of the distal segmental skeletal structures. We further show that genetic marking with a Prrx1:Cre-ERT2 driver marks a population of resident soft connective tissue cells that becomes enriched in the limb regenerate, thus identifying a key source
cell for skeletal regeneration.

Currently our efforts are focused on, understanding molecular cues that lead to limb regeneration. Through microarray and single cell transcriptomics analysis of connective tissue cells of mature limb, limb bud and blastema, we conclude that these cells acquire unique stage during blastema formation. We are now working towards, understanding the role of genes that were uniquely up-regulated during blastema formation. We hope that these efforts will improve our knowledge of limb development and regeneration and hopefully will lead to future therapies of wound healing.