Lola regulates Drosophila adult midgut homeostasis via non-canonical hippo signaling
Lola regulates Drosophila adult midgut homeostasis via non-canonical hippo signaling
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Lola 通过非经典河马信号调节果蝇成年中肠稳态
DOI：
10.7554/elife.47542
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发表时间：
2020-01-14
期刊：
影响因子：
7.7
通讯作者：
Zhang, Lei
中科院分区：
文献类型：
--
作者：
Hao, Xue;Wang, Shimin;Zhang, Lei
果蝇中肠组织的动态平衡和再生受到包括河马途径在内的多种信号通路的调控。河马信号通过将转录辅助因子yorkie(Yki)隔离在细胞质中来限制肠干细胞(ISC)的增殖，YKI是损伤诱导再生下ISC快速增殖所必需的因子。然而，Hippo介导的中肠内稳态的机制以及典型的Hippo信号是否参与ISC的基础增殖尚不清楚。在这里，我们确定LOLA是一个转录因子，作用于河马信号的下游，以一种不依赖yki的方式限制ISC的增殖。LOLA不仅与河马信号核心激酶疣(WTS)相互作用，并被WTS稳定，而且通过抑制DREF和SkpA的表达来拯救WTS耗竭时增强的ISC增殖。我们的发现表明，LOLA是一个非典型的河马信号成分，调节中肠的动态平衡，为组织维持和肠道功能的机制提供了见解。
Tissue homeostasis and regeneration in the Drosophila midgut is regulated by a diverse array of signaling pathways including the Hippo pathway. Hippo signaling restricts intestinal stem cell (ISC) proliferation by sequestering the transcription co-factor Yorkie (Yki) in the cytoplasm, a factor required for rapid ISC proliferation under injury-induced regeneration. Nonetheless, the mechanism of Hippo-mediated midgut homeostasis and whether canonical Hippo signaling is involved in ISC basal proliferation are less characterized. Here we identify Lola as a transcription factor acting downstream of Hippo signaling to restrict ISC proliferation in a Yki-independent manner. Not only that Lola interacts with and is stabilized by the Hippo signaling core kinase Warts (Wts), Lola rescues the enhanced ISC proliferation upon Wts depletion via suppressing Dref and SkpA expressions. Our findings reveal that Lola is a non-canonical Hippo signaling component in regulating midgut homeostasis, providing insights on the mechanism of tissue maintenance and intestinal function.