Identification of genes associated with regenerative success of Xenopus laevis hindlimbs

In the current study, we have taken advantage of the N1 transgenic line to directly compare morphology and gene expression in same stage regenerating vs. BMP signalling deficient non-regenerating hindlimb buds. The wound epithelium of N1 transgenic hindlimb buds, which forms over the cut surface of the limb bud after amputation, does not transition normally into the distal thickened apical epithelial cap. Instead, a basement membrane and dermis form, indicative of mature skin. Furthermore, the underlying mesenchyme remains rounded and does not expand to form a cone shaped blastema, a normal feature of successful regeneration.Using Affymetrix Gene Chip analysis, we have identified genes linked to regenerative success downstream of BMP signalling, including the BMP inhibitor Gremlin and the stress protein Hsp60 (no blastema in zebrafish). Gene Ontology analysis showed that genes involved in embryonic development and growth are significantly over-represented in regenerating early hindlimb buds and that successful regeneration in the Xenopus hindlimb correlates with the induction of stress response pathways.N1 transgenic hindlimbs, which do not regenerate, do not form an apical epithelial cap or cone shaped blastema following amputation. Comparison of gene expression in stage matched N1 vs. wild type hindlimb buds has revealed several new targets for regeneration research.While all vertebrates are capable of some types of tissue regeneration, most, including humans, have lost the ability to regenerate whole structures such as limbs (epimorphic regeneration), [1]. Amphibians, in contrast, are exceptionally good at it: adult urodeles (newts and salamanders) and larval anurans (frogs and toads) can regenerate limbs, tails, jaws, and, in some cases, even the lens of the eye [2]. Epimorphic regeneration can be thought of as occurring in two phases: wound healing and cell proliferation. Regeneration-competent wound healing of amphibian appendages is generally rapid and involv