Control mechanisms of mammalian limb regeneration potency

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Mammalian limbs do not regenerate except digit tip while the limbs of urodele amphibians regenerate completely. Xenopus, anuran amphibian, regenerate the limbs at larval stages, but the regeneration potency decreases during the course of metamorphosis and no limb regeneration occurs in the froglets. This temporal changes in the regeneration potency were found to be related to the expressions of fibroblast growth factor-10 gene (fgf-10) and sonic hedgehog gene (shh) in the limb bud mesenchyme(1,2).We examined the effects of FGFs an shh proteins on the amputated digit of mouse. Affigel beads presoaked in 1 mg/ml FGFs were applied in the amputated digit tips of mouse limb bud in organ culture. Cell proliferation in the region surrounding the beads was observed except those with FGF-8. The area of cartilage formation also increased, although no formation of distal cartilage elements was observed, suggesting that FGFs are necessary for the cartilage differentiation in the process of digit formation. No chondrogenic effect was observed in the digit tips with 1 mg/ml Shh protein. In neonatal mouse, digit tip was amputated at the first joint and FGF-beads were applied. The width of the amputated region increased but no formation of distal digit element was observed.Furthermore FGF-4 induced digit bifurcation in mouse limb bud, which suggests the role of FGF-4 in mouse limb pattern formation (3).