Wistar Institute, Philadelphia, PA 19104, USA.
Curr Top Microbiol Immunol. 2013;367:253-76. doi: 10.1007/82_2012_294.
Regeneration of ear punch holes in the MRL mouse and amputated limbs of the axolotl show a number of similarities. A large proportion of the fibroblasts of the uninjured MRL mouse ear are arrested in G2 of the cell cycle, and enter nerve-dependent mitosis after injury to form a ring-shaped blastema that regenerates the ear tissue. Multiple cell types contribute to the establishment of the regeneration blastema of the urodele limb by dedifferentiation, and there is substantial reason to believe that the cells of this early blastema are also arrested in G2, and enter mitosis under the influence of nerve-dependent factors supplied by the apical epidermal cap. Molecular analysis reveals other parallels, such as; (1) the upregulation of Evi5, a centrosomal protein that prevents mitosis by stabilizing Emi1, a protein that inhibits the degradation of cyclins by the anaphase promoting complex and (2) the expression of sodium channels by the epidermis. A central feature in the entry into the cell cycle by MRL ear fibroblasts is a natural downregulation of p21, and knockout of p21 in wild-type mice confers regenerative capacity on non-regenerating ear tissue. Whether the same is true for entry into the cell cycle in regenerating urodele limbs is presently unknown.
MRL 小鼠耳部穿孔的再生和蝾螈肢体的再生具有许多相似之处。未受伤的 MRL 小鼠耳部的大部分成纤维细胞在细胞周期的 G2 期停滞，并在受伤后进入神经依赖性有丝分裂，形成一个环形的胚基，从而再生耳部组织。多种细胞类型通过去分化参与了蝾螈肢体再生胚基的建立，有充分的理由相信这些早期胚基的细胞也在 G2 期停滞，并在由顶端表皮帽供应的神经依赖性因子的影响下进入有丝分裂。分子分析揭示了其他相似之处，例如：（1）中心体蛋白 Evi5 的上调，它通过稳定抑制细胞周期蛋白降解的复合物的 APC 来阻止有丝分裂；（2）表皮表达钠离子通道。MRL 耳部成纤维细胞进入细胞周期的一个主要特征是 p21 的自然下调，而在野生型小鼠中敲除 p21 则赋予了不能再生的耳部组织再生能力。在再生的蝾螈肢体中进入细胞周期是否也是如此，目前尚不清楚。
