A stepwise model system for limb regeneration

A stepwise model system for limb regeneration
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DOI:
10.1016/j.ydbio.2004.02.016
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发表时间:
2004-06-01
影响因子:
2.7
通讯作者:
Gardiner, DM
Gardiner, DM
中科院分区:
生物学3区
文献类型:
--
作者:
Endo, T;Bryant, SV;Gardiner, DM

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两栖动物的肢体是一个模型,它为组织和器官再生的原理和机制提供了许多见解。虽然肢体再生的后期阶段与肢体发育共享生长控制和模式化机制,但再生芽基的形成受再生所特有的早期事件控制。在这项研究中,我们提出了一个逐步的实验系统的基础上诱导肢体再生的皮肤伤口,这将允许识别和功能分析的分子控制这个早期,关键阶段的再生。如果神经偏离到肢体一侧的皮肤伤口,就会诱发异位芽基。如果将一片皮肤从肢体的对侧移植到伤口部位,同时伴有神经偏离,异位芽基继续生长并形成异位肢体。我们对真皮细胞迁移、贡献和增殖的分析表明,异位芽基相当于截肢后形成的芽基。需要来自神经的信号来诱导异位和正常芽基的形成,并且由来自肢体相对侧的芽基细胞提供的位置信息的多样性诱导生长和图案形成。因此,这种新的和方便的逐步模型允许发现必要的和足够的信号和条件,控制芽基的形成,生长,并在肢体再生的模式形成。(C)2004年爱思唯尔公司All rights reserved.
The amphibian limb is a model that has provided numerous insights into the principles and mechanisms of tissue and organ regeneration. While later stages of limb regeneration share mechanisms of growth control and patterning with limb development, the formation of a regeneration blastema is controlled by early events that are unique to regeneration. In this study, we present a stepwise experimental system based on induction of limb regeneration from skin wounds that will allow the identification and functional analysis of the molecules controlling this early, critical stage of regeneration. If a nerve is deviated to a skin wound on the side of a limb, an ectopic blastema is induced. If a piece of skin is grafted from the contralateral side of the limb to the wound site concomitantly with nerve deviation, the ectopic blastema continues to grow and forms an ectopic limb. Our analysis of dermal cell migration, contribution, and proliferation indicates that ectopic blastemas are equivalent to blastemas that form in response to limb amputation. Signals from nerves are required to induce formation of both ectopic and normal blastemas, and the diversity of positional information provided by blastema cells derived from opposite sides of the limb induces outgrowth and pattern formation. Hence, this novel and convenient stepwise model allows for the discovery of necessary and sufficient signals and conditions that control blastema formation, growth, and pattern formation during limb regeneration. (C) 2004 Elsevier Inc. All rights reserved.