Control mechanisms of mammalian limb regeneration potency

哺乳动物的肢体除趾尖外不再生，而有尾目两栖动物的肢体再生完全。无尾两栖动物非洲爪蟾在幼体阶段就能再生肢体，但在变态过程中再生能力下降，幼蛙没有肢体再生。发现再生能力的这种时间变化与肢芽间充质中成纤维细胞生长因子-10基因（FGF-10）和音刺猬基因（shh）的表达有关（1，2）。在器官培养中，将预先浸泡在lmg/ml FGF中的Affigel珠应用于小鼠肢芽的截肢指尖。除了具有FGF-8的珠粒之外，观察到珠粒周围区域中的细胞增殖。软骨形成的面积也增加了，虽然没有观察到远端软骨成分的形成，这表明FGF是指形成过程中软骨分化所必需的。在具有lmg/ml Shh蛋白的指尖中未观察到软骨形成效应。在新生小鼠中，在第一关节处截去趾尖并施加FGF珠。此外，FGF-4诱导小鼠肢芽中的趾分叉，这表明FGF-4在小鼠肢模式形成中的作用（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).