IGF signaling between blastema and wound epidermis is required for fin regeneration
IGF signaling between blastema and wound epidermis is required for fin regeneration
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DOI：
10.1242/dev.043885
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发表时间：
2010-03-15
期刊：
影响因子：
4.6
通讯作者：
Jazwinska, Anna
中科院分区：
文献类型：
--
作者：
Chablais, Fabian;Jazwinska, Anna
在哺乳动物中，失去肢体是不可逆转的。相比之下，尾纲两栖动物和硬骨鱼能够几乎完美地再生失去的附属物。这种能力依赖于创面上皮和胚间充质祖细胞之间的直接相互作用。几十年来，人们已经知道伤口上皮和下层胚间的接触是成功再生的必要条件。然而，人们对其潜在机制知之甚少。在这里，我们发现在截肢后，胚基诱导配体Igf2b的表达，然后在邻近的顶端上皮细胞中特异性地激活IGF信号。通过morpholino反义技术或Igf1受体功能的特异性化学抑制剂NVP-AEW541和NVP-ADW742抑制IGF信号传导，都会损害鳍的再生。在细胞水平上，这种再生障碍反映在缺乏独特的基底上皮，伤口表皮细胞凋亡增加和囊胚细胞增殖减少。此外，在缺乏IGF信号的情况下，不能支持胚质和创面表皮标记物的诱导。这些数据表明，Igf2b在胚芽中表达促进了邻近创面表皮的特性，这是胚芽功能所必需的。因此，IGF信号在断肢时的上调代表了一个从胚基到伤口上皮的信号，这是附件再生的关键步骤。
In mammals, the loss of a limb is irreversible. By contrast, urodele amphibians and teleost fish are capable of nearly perfect regeneration of lost appendages. This ability depends on direct interaction between the wound epithelium and mesenchymal progenitor cells of the blastema. It has been known for decades that contact between the wound epithelium and the underlying blastema is essential for successful regeneration. However, the underlying mechanisms are poorly understood. Here, we show that upon amputation the blastema induces expression of the ligand Igf2b, which then activates IGF signaling specifically in cells of the adjacent apical epithelium. Inhibition of IGF signaling by either morpholino antisense technology, or by specific chemical inhibitors of Igf1 receptor function NVP-AEW541 and NVP-ADW742, impairs fin regeneration. At the cellular level, this block in regeneration is reflected by a lack of the distinctive basal epithelium, increased apoptosis in the wound epidermis and reduced proliferation of blastema cells. Furthermore, induction of the blastemal and wound epidermal markers cannot be supported in the absence of IGF signaling. These data provide evidence that Igf2b expressed in the blastema promotes the properties of the adjacent wound epidermis, which subsequently are necessary for blastema function. Thus, IGF signaling upregulated upon fin amputation represents a signal from the blastema to the wound epithelium, a crucial step in appendage regeneration.