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BMC Dev Biol July 28, 2008; 8 66.

Identification of genes associated with regenerative success of Xenopus laevis hindlimbs.

Pearl EJ , Barker D , Day RC , Beck CW .

Epimorphic regeneration is the process by which complete regeneration of a complex structure such as a limb occurs through production of a proliferating blastema. This type of regeneration is rare among vertebrates but does occur in the African clawed frog Xenopus laevis, traditionally a model organism for the study of early development. Xenopus tadpoles can regenerate their tails, limb buds and the lens of the eye, although the ability of the latter two organs to regenerate diminishes with advancing developmental stage. Using a heat shock inducible transgene that remains silent unless activated, we have established a stable line of transgenic Xenopus (strain N1) in which the BMP inhibitor Noggin can be over-expressed at any time during development. Activation of this transgene blocks regeneration of the tail and limb of Xenopus tadpoles. 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.

PubMed ID: 18570684
PMC ID: PMC2483965
Article link: BMC Dev Biol

Species referenced: Xenopus
Genes referenced: adh1 aldh1a2 azin2 ca2 col9a1 col9a3 exosc9 grem1 hba1 hsp90aa1.1 hsp90b1 hspd1 krt18.1 map1lc3a mt4 nog npm3 olfm4 ptgs2 thbs4 timm22 tmprss2.6

GEO Series: GSE9813: NCBI
Phenotypes: Xla.Tg(hsp70:nog,cryga:GFP) + hindlimb bud amputation + HS (Fig. 1 F,F') [+]

Article Images: [+] show captions
References [+] :
Ahn, BMPR-IA signaling is required for the formation of the apical ectodermal ridge and dorsal-ventral patterning of the limb. 2001, Pubmed