In limb development, limb formation starts from limb buds that are tiny and almost identical in size, whereas limb regeneration begins from structures of varying sizes, depending on the size of the amputated limb. A remarkable feature of this process is the ability to regenerate normal limb morphology and anatomical patterning from the blastema - the early regeneration primordial tissue. While it is thought that regeneration uses similar molecular mechanisms to those employed during development, it is not well understood how this is achieved in the context of varying blastema size. Here, Akira Satoh, Yoshihiro Morishita and their team examine the relationship between the blastema size and gene expression patterns for Sonic Hedgehog (Shh) and Fibroblast Growth Factor 8 (Fgf8), both of which play key roles in limb growth and patterning. They find that while blastema size scales allometrically (disproportionately) with limb stump size, the ratio of Shh to Fgf8 signaling regions remains consistent, regardless of size. Additionally, the spatial patterns of cell density and proliferation, and the first point of digit formation also exhibit scale invariance. Overall, these findings suggest that scale-invariant mechanisms are crucial for the ability of the axolotl ability to regenerate limbs of different sizes while maintaining normal limb morphology.
