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Review: Regeneration of the tail in lizards appears regulated by a balanced expression of oncogenes and tumor suppressors
Annals of Anatomy ( IF 2.0 ) Pub Date : 2021-08-31 , DOI: 10.1016/j.aanat.2021.151824
Lorenzo Alibardi 1
Affiliation  

Background

Tail regeneration in lizards is the only case of large multi-tissue organ regeneration in amniotes.

Methods

The present Review summarizes numerous immunolocalization and gene-expression studies indicating that after tail amputation in lizards the stump is covered in 7–10 days by the migration of keratinocytes. This allows the accumulation of mesenchymal-fibroblasts underneath the wound epidermis and forms a regenerative blastema and a new tail.

Results

During migration keratinocytes transit from a compact epidermis into relatively free keratinocytes in a process of “Epithelial Mesenchymal Transition” (EMT). While EMT has been implicated in carcinogenesis no malignant transformation is observed during these cell movements in the regenerative blastema. Immunolabeling for E-cadherin and snail shows that these proteins are present in the cytoplasm and nuclei of migrating keratinocytes. The basal layer of the wound epithelium of the apical blastema express onco-proteins (wnt2b, egfr, c-myc, fgfs, fgfr, rhov, etc.) and tumor suppressors (p53/63, fat2, ephr, apc, retinoblastoma, arhgap28 etc.). This suggests that their balanced action regulates proliferation of the blastema.

Conclusions

While apical epidermis and mesenchyme are kept under a tight proliferative control, in more proximal regions of the regenerating tail the expression of tumor-suppressors triggers the differentiation of numerous tissues, forming the large myomeres, axial cartilage, simple spinal cord and nerves, new scales, arteries and veins, fat deposits, dermis and other connective tissues. Understanding gene expression patterns of developmental pathways activated during tail regeneration in lizards is useful for cancer research and for future attempts to induce organ regeneration in other amniotes including humans.



中文翻译:

评论:蜥蜴尾巴的再生似乎受到癌基因和肿瘤抑制因子的平衡表达的调节

背景

蜥蜴的尾巴再生是羊膜动物中大型多组织器官再生的唯一案例。

方法

本综述总结了大量免疫定位和基因表达研究,表明在蜥蜴的尾巴截肢后,角化细胞的迁移在 7-10 天内覆盖了残端。这允许间充质成纤维细胞在伤口表皮下方积累并形成再生胚芽和新尾巴。

结果

在迁移过程中,角质形成细胞在“上皮间质转化”(EMT)的过程中从致密的表皮过渡到相对游离的角质形成细胞。虽然 EMT 与癌发生有关,但在再生胚泡中的这些细胞运动期间未观察到恶性转化。E-钙粘蛋白和蜗牛的免疫标记表明这些蛋白质存在于迁移的角质形成细胞的细胞质和细胞核中。顶端胚泡的伤口上皮基底层表达癌蛋白(wnt2b、egfr、c-myc、fgfs、fgfr、rhov 等)和肿瘤抑制因子(p53/63、fat2、ephr、apc、视网膜母细胞瘤、arhgap28 ETC。)。这表明它们的平衡作用调节了胚泡的增殖。

结论

虽然顶端表皮和间充质受到严格的增殖控制,但在再生尾部的更近端区域,肿瘤抑制因子的表达触发了许多组织的分化,形成了大肌球、轴向软骨、简单的脊髓和神经、新的鳞片、动脉和静脉、脂肪沉积、真皮和其他结缔组织。了解蜥蜴尾巴再生过程中激活的发育途径的基因表达模式对于癌症研究和未来在包括人类在内的其他羊膜动物中诱导器官再生的尝试很有用。

更新日期:2021-09-28
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