Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila.

Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila.
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DOI:
10.1038/emboj.2012.248
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发表时间:
2012-10-03
期刊:
影响因子:
11.4
通讯作者:
Sansom, Owen J.
Sansom, Owen J.
中科院分区:
生物学1区
文献类型:
--
作者:
Cordero, Julia B.;Stefanatos, Rhoda K.;Scopelliti, Alessandro;Vidal, Marcos;Sansom, Owen J.

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在压力下再生的能力是自我更新组织的标志。然而,很少有人知道如何再生不同于稳态组织维护。在这里,我们研究的作用和调节无翅(Wg)/Wnt信号在肠道再生果蝇成年中肠。我们表明,Wg是由肠上皮细胞室损伤或应力时,它是专门需要肠干细胞(ISC)增殖组织再生。减少Wg或来自肠上皮的下游信号传导组分阻断了组织再生。重要的是,我们证明,Wg从未分化的祖细胞,肠母细胞,是所需的Myc依赖的ISC增殖再生过程中。与年轻的再生组织类似,老化的肠需要Wg和Myc用于ISC过度增殖。出乎意料的是,我们的研究结果表明,上皮而不是间充质Wg是必要的ISC增殖响应损伤,而不是源的配体是唯一负责ISC的维护和组织自我更新在未受到挑战的组织。因此,微调Wnt导致对压力的反应能力之间的最佳平衡,而不会对生物体的生存能力产生负面影响。
The ability to regenerate following stress is a hallmark of self-renewing tissues. However, little is known about how regeneration differs from homeostatic tissue maintenance. Here, we study the role and regulation of Wingless (Wg)/Wnt signalling during intestinal regeneration using the Drosophila adult midgut. We show that Wg is produced by the intestinal epithelial compartment upon damage or stress and it is exclusively required for intestinal stem cell (ISC) proliferation during tissue regeneration. Reducing Wg or downstream signalling components from the intestinal epithelium blocked tissue regeneration. Importantly, we demonstrate that Wg from the undifferentiated progenitor cell, the enteroblast, is required for Myc-dependent ISC proliferation during regeneration. Similar to young regenerating tissues, ageing intestines required Wg and Myc for ISC hyperproliferation. Unexpectedly, our results demonstrate that epithelial but not mesenchymal Wg is essential for ISC proliferation in response to damage, while neither source of the ligand is solely responsible for ISC maintenance and tissue self-renewal in unchallenged tissues. Therefore, fine-tuning Wnt results in optimal balance between the ability to respond to stress without negatively affecting organismal viability.
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