The hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity.

The hippo pathway promotes Notch signaling in regulation of cell differentiation, proliferation, and oocyte polarity.
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河马途径在调节细胞分化,增殖和卵母细胞极性方面促进了缺口信号。

DOI:
10.1371/journal.pone.0001761
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发表时间:
2008-03-12
期刊:
影响因子:
3.7
通讯作者:
Deng WM
Deng WM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yu J;Poulton J;Huang YC;Deng WM

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果蝇卵母细胞前后轴的特化需要生殖系细胞和体细胞来源的滤泡上皮细胞之间的适当沟通。包括Notch在内的多种信号通路通过控制卵泡细胞分化和增殖的时间和空间模式来促进卵母细胞极性的形成。在这里,我们表明,新发现的河马肿瘤抑制通路在后卵泡细胞中起着至关重要的作用,在卵母细胞极性的调节。Hippo通路(包括主要组分Hippo、萨尔瓦多和疣)的破坏导致异常卵泡细胞分化和增殖以及卵母细胞前后轴的显著破坏。这些表型与卵泡细胞中缺陷的Notch信号传导有关,因为Notch的组成性活性形式的错误表达会导致卵母细胞极性缺陷。我们还发现Hippo信号缺陷的卵泡细胞积累Notch受体,并显示内吞标记缺陷。我们的研究结果表明,河马和经典的发展途径,如Notch之间的相互作用是至关重要的空间和时间调节的分化和增殖,是必不可少的果蝇体轴的发展。
Specification of the anterior-posterior axis in Drosophila oocytes requires proper communication between the germ-line cells and the somatically derived follicular epithelial cells. Multiple signaling pathways, including Notch, contribute to oocyte polarity formation by controlling the temporal and spatial pattern of follicle cell differentiation and proliferation. Here we show that the newly identified Hippo tumor-suppressor pathway plays a crucial role in the posterior follicle cells in the regulation of oocyte polarity. Disruption of the Hippo pathway, including major components Hippo, Salvador, and Warts, results in aberrant follicle-cell differentiation and proliferation and dramatic disruption of the oocyte anterior-posterior axis. These phenotypes are related to defective Notch signaling in follicle cells, because misexpression of a constitutively active form of Notch alleviates the oocyte polarity defects. We also find that follicle cells defective in Hippo signaling accumulate the Notch receptor and display defects in endocytosis markers. Our findings suggest that the interaction between Hippo and classic developmental pathways such as Notch is critical to spatial and temporal regulation of differentiation and proliferation and is essential for development of the body axes in Drosophila.
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