Shh expression in developing and regenerating limb buds ofXenopus laevis

Mechanisms of urodele limb regeneration

“…Xenopus limbs, like other tetrapod limbs, develop in posterior to anterior order (Keenan & Beck, 2016; Stopper & Wagner, 2005), and contain a posterior mesenchymal polarizing zone expressing Shh (Cameron & Fallon, 1977; Endo, Yokoyama, Tamura, & Ide, 1997). In these limb buds, the shh enhancer is hypomethylated and shh is expressed, but becomes hypermethylated in late tadpole limbs with loss of shh expression, which is correlated with regeneration of only a cartilaginous spike (Yakushiji et al., 2007).…”

Looking proximally and distally: 100 years of limb regeneration and beyond

“…Studies on such changes have begun for newt lens regeneration Nakamura et al, 2010) but have not yet been reported for limb regeneration beyond the observation that the long-range limb-specific shh enhancer, a conserved sequence called mammals-fishes-conserved-sequence 1 (MFCS1), which is located in a non-coding region of the LMBR1 gene (Sagai et al, 2004), is hypermethylated in Xenopus versus moderately methylated in the axolotl and newt (Yakushiji et al, 2007). This hypermethylation is associated with the lack of shh expression and formation of a cartilage rod by the fibroblastema of the amputated Xenopus limb Yakushiji et al, 2007), in contrast to the expression of shh in the posterior tissue of the urodele limb regeneration blastema Yoshizato, 1997, 1998;Endo et al, 1997;Torok et al, 1999).…”

“…The effector molecule of the ZPA is sonic hedgehog (Shh) (Riddle et al, 1993). Shh expression was demonstrated in the posterior blastema tissue of newt and Xenopus early tadpole limbs, as well as in posterior stump tissue following reversal of the blastema AP axis by contralateral grafting Yoshizato, 1997, 1998;Endo et al, 1997;Torok et al, 1999). Furthermore, the transfection of Shh into anterior blastema tissue by vaccinia virus to posteriorize anterior cells and set up an AP confrontation resulted in the production of a supernumerary limb (Roy et al, 2000).…”

“…The model proposes that these interactions result in the production of a morphogen that spreads out from the intersection point. However, whether such a morphogen exists or whether the ZPA actually has a role in the initial interactions that result in regeneration needs further investigation, because no intersect morphogen has been identified, and shh expression does not occur until the conical (medium bud) stage of regeneration Yoshizato, 1997, 1998;Endo et al, 1997). Nevertheless, an analysis by Maden (1983) showed that the boundary model not only correctly predicted the handedness and position of supernumeraries regenerated after blastema AP and DV reversal, but most of the anatomical classes of supernumeraries created by APDV reversal, the hypomorphic regeneration of double anterior limbs, and the symmetrical, PD-complete regeneration of double posterior limbs.…”

The molecular basis of amphibian limb regeneration: integrating the old with the new

“…Loss of regenerative ability occurs progressively, 28,29 and is associated with the progressive loss of the ability to reexpress genes involved in growth and pattern formation (e.g. shh 30 ). During this period, regenerative ability can be rescued to a limited extent by the application of exogenous FGF (FGF2 and FGF4 in chick and FGF10 in Xenopus (see References 31,32).…”