The aneurogenic limb identifies developmental cell interactions underlying vertebrate limb regeneration
The aneurogenic limb identifies developmental cell interactions underlying vertebrate limb regeneration
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DOI：
10.1073/pnas.1108472108
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发表时间：
2011-08-16
影响因子：
11.1
通讯作者：
Brockes, Jeremy P.
中科院分区：
文献类型：
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作者：
Kumar, Anoop;Delgado, Jean-Paul;Brockes, Jeremy P.
去除蝾螈胚胎中的神经管可以发育出无神经的无神经肢体。肢体再生通常是神经依赖性的，但无神经的肢体再生没有神经，神经支配后成为神经依赖性的。这些组织相互作用的分子基础尚不清楚。前梯度（AG）蛋白，以前显示，以拯救再生失神经支配的肢体，并作为一种生长因子培养的肢体胚细胞，整个幼虫肢体表皮表达，并下调神经支配。在致神经瘤的肢体中，AG蛋白的水平在整个发育和再生过程中在表皮中保持高水平，但在移植到正常宿主后的神经支配后降低。非神经原性表皮也显示出分泌腺细胞的五倍差异，其表达AG蛋白。AG在致神经瘤肢体的上皮细胞中的持续高表达确保了再生不依赖于神经。这些研究结果提供了一个解释这个经典的问题，并确定调节表皮生态位的神经支配作为一个独特的发展机制，启动神经依赖的肢体再生。在无尾类动物肢体发育过程中缺乏这种调节可能表明它与肢体再生有关。
The removal of the neural tube in salamander embryos allows the development of nerve-free aneurogenic limbs. Limb regeneration is normally nerve-dependent, but the aneurogenic limb regenerates without nerves and becomes nerve-dependent after innervation. The molecular basis for these tissue interactions is unclear. Anterior Gradient (AG) protein, previously shown to rescue regeneration of denervated limbs and to act as a growth factor for cultured limb blastemal cells, is expressed throughout the larval limb epidermis and is down-regulated by innervation. In an aneurogenic limb, the level of AG protein remains high in the epidermis throughout development and regeneration, but decreases after innervation following transplantation to a normal host. Aneurogenic epidermis also shows a fivefold difference in secretory gland cells, which express AG protein. The persistently high expression of AG in the epithelial cells of an aneurogenic limb ensures that regeneration is independent of the nerve. These findings provide an explanation for this classical problem, and identify regulation of the epidermal niche by innervation as a distinctive developmental mechanism that initiates the nerve dependence of limb regeneration. The absence of this regulation during anuran limb development might suggest that it evolved in relation to limb regeneration.