Retinoic acid and thyroid hormone may function through similar and competitive pathways in regenerating axolotls

The objective of this study was to determine whether thyroid hormone (TH) would interfere with retinoic acid (RA), which proximalizes axolotl larvae regenerate limb pattern. RA and TH are ligands for members of the steroid hormone thyroid hormone nuclear binding protein superfamily which form functional homodimers, but may also form stable heterodimers with the RXR protein and may recognize identical DNA sequences. TH alone does not affect limb pattern but induces metamorphosis in regenerating animals. Coinjected animals do not metamorphose, and when compared to RA controls regenerate more proximal and in some cases anteroposterior (AP) and dorsoventral (DV) duplicate limb structures. In addition, the tissues that are normally lost or changed during metamorphosis appear to be sensitized resulting in the formation of (1) new dorsal gill lamellae accompanied by bifurcation and broadening of the original gill lamellae, (2) partial resorption of the tail fin, and (3) changes in eye position and snout morphology. Bifurcation of gill lamellae tips, but not the formation of supernumerary gills, is also observed in animals treated with RA alone. These results indicate that the molecular mechanism of RA and TH function through similar and perhaps competitive pathways.