Department of Biology and Center for Regenerative Biology and Medicine, Indiana University-Purdue University Indianapolis, 723 W. Michigan St, Indianapolis, IN 46202, USA.
Eur J Neurosci. 2011 Sep;34(6):908-16. doi: 10.1111/j.1460-9568.2011.07827.x.
Nerve axons and the apical epidermal cap (AEC) are both essential for the formation of an accumulation blastema by amputated limbs of urodele salamanders. The AEC forms in the absence of axons, but is not maintained, and blastema formation fails. Growth stages of the blastema become nerve-independent for morphogenesis, but remain dependent on the nerve for blastema growth. Denervated growth stage blastemas form smaller than normal skeletal parts, owing to diminished mitosis, but form the full proximodistal array of skeletal elements. This difference in nerve dependency of morphogenesis and proliferation is hypothesized to be the result of a dependence of the AEC on nerves for blastema cell proliferation but not for blastema morphogenesis. Regenerating axons induce the synthesis and secretion of the anterior gradient protein (AGP) by distal Schwann cells during dedifferentiation and by the gland cells of the AEC during blastema growth stages. AGP promotes the regeneration of a denervated limb to digit stages when electroporated into the limb during dedifferentiation. Once a critical mass of blastema cells has been attained, the blastema can undergo morphogenesis in the absence of the nerve, but the regenerate will be a miniature, because the nerve is no longer inducing the AEC to carry out its AGP-mediated proliferative function. AGP expression by both Schwann cells and the AEC is induced by axons, but the nature of the inductive agent is unclear.
轴突和顶端表皮帽（AEC）对于蝾螈肢体切除后积累性芽基的形成都是必不可少的。AEC 在没有轴突的情况下形成，但不能维持，芽基形成失败。芽基的生长阶段在形态发生方面变得不依赖于神经，但仍然依赖于神经来维持芽基的生长。去神经的生长阶段芽基形成的骨骼部分比正常的小，这是由于有丝分裂减少，但形成了完整的近-远轴骨骼元素排列。形态发生和增殖的神经依赖性的这种差异，据推测是由于 AEC 依赖于神经来促进芽基细胞增殖，但不依赖于神经来促进芽基形态发生。再生轴突在去分化期间诱导远端施万细胞合成和分泌前梯度蛋白（AGP），并在芽基生长阶段诱导 AEC 的腺细胞合成和分泌 AGP。当 AGP 在去分化期间电转染到肢体中时，它可以促进去神经肢体再生到指节阶段。一旦达到临界数量的芽基细胞，芽基就可以在没有神经的情况下进行形态发生，但再生的肢体将是一个小型的，因为神经不再诱导 AEC 发挥其 AGP 介导的增殖功能。施万细胞和 AEC 中的 AGP 表达均受轴突诱导，但诱导剂的性质尚不清楚。
