Control mechanisms of mammalian limb regeneration potency

哺乳动物四肢除趾尖外不能再生，而尾纲两栖动物四肢可完全再生。爪蟾是一种无尾两栖动物，在幼虫期可以再生肢体，但在蜕变过程中再生能力下降，在幼崽中不发生肢体再生。这种再生能力的时间变化被发现与成纤维细胞生长因子-10基因（fgf-10）和超音hedgehog基因（shh）在肢芽间质中的表达有关（1,2）。我们研究了FGFs和shh蛋白对小鼠断指的影响。将1 mg/ml FGFs预浸过的Affigel微珠应用于器官培养小鼠断指尖肢芽。除含有FGF-8的外，其余细胞均有增殖。虽然没有观察到远端软骨分子的形成，但软骨形成的面积也增加了，这表明在手指形成过程中，FGFs是软骨分化所必需的。1 mg/ml Shh蛋白对指尖无软骨形成作用。在新生小鼠的第一个关节处切除手指尖端，并应用fgf珠。截肢区宽度增加，但未见远端指骨形成。此外，FGF-4在小鼠肢体芽中诱导手指分叉，这表明FGF-4在小鼠肢体模式形成中的作用(3)。

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).