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.

中文翻译：

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萝拉通过非规范性河马信号调节果蝇成虫中肠稳态

果蝇的组织稳态与再生中肠受包括Hippo途径在内的多种信号传导途径的调控。河马信号传导通过隔离细胞质中的转录辅助因子Yorkie（Yki）来限制肠道干细胞（ISC）的增殖，这是在损伤诱导的再生下快速ISC增殖所需的因子。但是，河马介导的中肠稳态和ISC基础增殖是否参与了典型的河马信号传导机制尚不清楚。在这里，我们确定萝拉是转录因子，在河马信号下游起作用，以独立于Yki的方式限制ISC增殖。Lola不仅与Hippo信号转导核心激酶疣（Wts）相互作用并被其稳定，而且Lola通过抑制Dref和Href拯救Wts耗尽时增强的ISC增殖。SkpA表达式。我们的发现表明，Lola是调节中肠稳态的非典型Hippo信号传导成分，可提供有关组织维持和肠道功能机制的见解。