Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection.
Drosophila EGFR pathway coordinates stem cell proliferation and gut remodeling following infection.
复制标题
DOI：
10.1186/1741-7007-8-152
复制
发表时间：
2010-12-22
期刊：
影响因子：
5.4
通讯作者：
Lemaitre B
中科院分区：
文献类型：
--
作者：
Buchon N;Broderick NA;Kuraishi T;Lemaitre B
肠道内稳态是整个生物体健康的核心，其破坏与广泛的病理学有关。损伤后，肠道需要复杂的生理事件来维持适当的稳态。以前，我们证明了摄入一种非致死性病原体，Erwinia carotovora carotovora 15，诱导果蝇肠道干细胞增殖的大量增加。然而，感染后发生的精确细胞事件尚未定量描述，我们也不了解上皮更新中涉及的多种途径之间的相互作用。为了更详细地了解感染和上皮更新的过程，我们对肠道的几种细胞和形态特征进行了定量分析。我们观察到成年果蝇的肠道在细菌感染后发生动态重塑。这种重塑协调了新肠细胞的合成、它们的适当形态发生以及通过分层和失巢凋亡消除受损细胞。我们证明，一个信号通路，表皮生长因子受体（EGFR）通路，是通过在肠干细胞和肠上皮细胞中的不同功能来控制这些步骤的关键。EGFR途径由EGF配体Spitz、Keren和Vein激活，后者部分在Janus激酶/信号转导和转录激活因子（JAK/STAT）途径的控制下在周围内脏肌肉中诱导。此外，EGFR途径与干细胞中的JAK/STAT途径协同作用以促进其增殖。最后，我们表明，EGFR途径有助于肠道形态通过其在肠上皮细胞中的活动，并需要适当协调受损细胞的分层和失巢凋亡。肠上皮细胞中EGFR途径的这种功能是维持体内平衡的关键，因为缺乏EGFR的果蝇对感染高度敏感。这项研究表明，细菌感染后恢复正常肠道形态是一个比以前描述的更复杂的现象。维持肠道稳态需要协调干细胞增殖和分化，新细胞的掺入和形态发生以及受损肠细胞的排出。我们表明，一种信号通路，即EGFR通路，是所有这些阶段的核心，它在多个步骤的激活可以同步复杂的细胞事件，从而导致肠道修复和体内平衡。
Gut homeostasis is central to whole organism health, and its disruption is associated with a broad range of pathologies. Following damage, complex physiological events are required in the gut to maintain proper homeostasis. Previously, we demonstrated that ingestion of a nonlethal pathogen, Erwinia carotovora carotovora 15, induces a massive increase in stem cell proliferation in the gut of Drosophila. However, the precise cellular events that occur following infection have not been quantitatively described, nor do we understand the interaction between multiple pathways that have been implicated in epithelium renewal. To understand the process of infection and epithelium renewal in more detail, we performed a quantitative analysis of several cellular and morphological characteristics of the gut. We observed that the gut of adult Drosophila undergoes a dynamic remodeling in response to bacterial infection. This remodeling coordinates the synthesis of new enterocytes, their proper morphogenesis and the elimination of damaged cells through delamination and anoikis. We demonstrate that one signaling pathway, the epidermal growth factor receptor (EGFR) pathway, is key to controlling each of these steps through distinct functions in intestinal stem cells and enterocytes. The EGFR pathway is activated by the EGF ligands, Spitz, Keren and Vein, the latter being induced in the surrounding visceral muscles in part under the control of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Additionally, the EGFR pathway synergizes with the JAK/STAT pathway in stem cells to promote their proliferation. Finally, we show that the EGFR pathway contributes to gut morphogenesis through its activity in enterocytes and is required to properly coordinate the delamination and anoikis of damaged cells. This function of the EGFR pathway in enterocytes is key to maintaining homeostasis, as flies lacking EGFR are highly susceptible to infection. This study demonstrates that restoration of normal gut morphology following bacterial infection is a more complex phenomenon than previously described. Maintenance of gut homeostasis requires the coordination of stem cell proliferation and differentiation, with the incorporation and morphogenesis of new cells and the expulsion of damaged enterocytes. We show that one signaling pathway, the EGFR pathway, is central to all these stages, and its activation at multiple steps could synchronize the complex cellular events leading to gut repair and homeostasis.
登录
查看更多内容
影响因子：
1.2
作者：
Bach, Erika A.;Ekas, Laura A.;Baeg, Gyeong-Hun
通讯作者：
Baeg, Gyeong-Hun
DOI：
10.1073/pnas.070357597
发表时间：
2000-03-28
影响因子：
11.1
作者：
Basset, A;Khush, RS;Lemaitre, B
通讯作者：
Lemaitre, B
影响因子：
2.7
作者：
Beebe, Katherine;Lee, Wen-Chih;Micchelli, Craig A.
通讯作者：
Micchelli, Craig A.
影响因子：
11.8
作者：
Li, JH;Xia, F;Li, X
通讯作者：
Li, X
影响因子：
2.7
作者：
Brown, Katherine E.;Baonza, Antonio;Freeman, Matthew
通讯作者：
Freeman, Matthew