Abstract

Among tetrapods, the salamanders show a remarkable ability to regenerate complex body parts including the limb where the entire, patterned limb skeleton and all other tissues are faithfully reconstructed after limb amputation. In contrast, the frog shows only partial regeneration of a cartilage rod, and mammals show no limb regeneration except the very tip of the digit. We have been using molecular biology and protein biochemistry approaches to define the extracellular cues that induce limb regeneration. While in most cases, orthologous signalling proteins show homologous function, it appears that one important initiating molecule, MARCKS -Like Protein, shows species specific activities. I will discuss our work on this protein. We have also turned to single cell sequencing to understand the molecular progression of regeneration in the axolotl, and to compare the cell states that occur to those in abortive frog regeneration. Through combination of transcriptome analysis and cell transplantation, we have asked whether the limitation in frog regeneration is due to humoral, systemic factors or due to intrinsic limitation in limb cell potential.