Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation
Ci antagonizes Hippo signaling in the somatic cells of the ovary to drive germline stem cell differentiation
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Ci 拮抗卵巢体细胞中的 Hippo 信号传导以驱动生殖干细胞分化
DOI：
10.1038/cr.2015.114
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发表时间：
2015-10-01
期刊：
影响因子：
44.1
通讯作者：
Chen, Dahua
中科院分区：
文献类型：
--
作者：
Li, Chaoyi;Kan, Lijuan;Chen, Dahua
许多干细胞群受到其局部微环境（生态位）的严格调控，其中包括不同类型的基质细胞。然而，关于小生境亚群协调决定干细胞命运的机制知之甚少。本研究发现，Hippo通路的关键组分Yki在果蝇卵巢中护航细胞（EC）促进种系分化的功能中起着至关重要的作用。我们发现主要来自帽细胞的Hedgehog （Hh）信号支持ECs的功能，其中Hh信号效应Cubitus interruptus （Ci）可抑制Hippo激酶级联活性。在机制上，我们发现Ci竞争性地与Hpo相互作用并损害Hpo- wts信号复合物的形成，从而促进Yki核定位。Ci的作用确保了Yki信号有效地对抗Sd/Tgi/ vg介导的ECs默认抑制。本研究揭示了小生境细胞亚群如何通过Hh-Hippo信号串扰协调决定干细胞命运的机制，并增强了我们对致癌Yki/YAP信号的机制调控的理解。
Many stem cell populations are tightly regulated by their local microenvironment (niche), which comprises distinct types of stromal cells. However, little is known about mechanisms by which niche subgroups coordinately determine the stem cell fate. Here we identify that Yki, the key Hippo pathway component, is essential for escort cell (EC) function in promoting germline differentiation in Drosophila ovary. We found that Hedgehog (Hh) signals emanating primarily from cap cells support the function of ECs, where Cubitus interruptus (Ci), the Hh signaling effector, acts to inhibit Hippo kinase cascade activity. Mechanistically, we found that Ci competitively interacts with Hpo and impairs the Hpo-Wts signaling complex formation, thereby promoting Yki nuclear localization. The actions of Ci ensure effective Yki signaling to antagonize Sd/Tgi/Vg-mediated default repression in ECs. This study uncovers a mechanism explaining how subgroups of niche cells coordinate to determine the stem cell fate via Hh-Hippo signaling crosstalk, and enhances our understanding of mechanistic regulations of the oncogenic Yki/YAP signaling.