Hedgehog and Wnt Signaling Pathways Regulate Tail Regeneration

Urodele amphibians have a tremendous capacity for the regeneration of appendages, including limb and tail, following injury. While studies have focused on the cellular and morphological changes during appendicular regeneration, the signaling mechanisms that govern these cytoarchitectural changes during the regenerative response are unclear. In this study, we describe the essential role of hedgehog (Hh) and Wnt signaling pathways following tail amputation in the newt. Quantitative PCR studies revealed that members of both the Hh and Wnt signaling pathways, including the following: shh, ihh, ptc-1, wnt-3a, β-catenin, axin2, frizzled (frzd)-1, and frzd-2 transcripts, were induced following injury. Continuous pharmacological-mediated inhibition of Hh signaling resulted in spike-like regenerates with no evidence of tissue patterning, whereas activation of Hh signaling enhanced the regenerative process. Pharmacological-mediated temporal inhibition experiments demonstrated that the Hh-mediated patterning of the ...