Salvador-Warts-Hippo pathway regulates sensory organ development via caspase-dependent nonapoptotic signaling
Salvador-Warts-Hippo pathway regulates sensory organ development via caspase-dependent nonapoptotic signaling
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DOI：
10.1038/s41419-019-1924-3
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发表时间：
2019-09-11
影响因子：
9
通讯作者：
Baker, Nicholas E.
中科院分区：
文献类型：
--
作者：
Wang, Lan-Hsin;Baker, Nicholas E.
Salvador-Warts-Hippo (SWH) 通路的基本作用在生长调节和器官大小控制方面具有广泛的特征。然而，SWH 通路在细胞命运决定中的功能却鲜为人知。在这里，我们发现了 SWH 信号通路在神经前体（感觉器官前体，SOP）发育过程中决定细胞命运的新作用。翅成虫盘 SOP 中 SWH 通路的失活会影响细胞凋亡无关过程中依赖于 caspase 的刚毛图案。半胱天冬酶的这种非凋亡功能与炎症、增殖、细胞重塑和细胞命运决定有关。我们的数据表明对 Wingless (Wg)/Wnt 途径有影响。此前，半胱天冬酶被认为可以裂解并激活 Wg/Wnt 信号传导的负调节因子 Shaggy (Sgg)/GSK3 beta。令人惊讶的是，我们发现 CRISPR-Cas9 修饰后内源基因座编码的不可切割形式的 Sgg 支持几乎正常的鬃毛图案，表明 Sgg 可能不是 caspase 依赖性非凋亡过程的主要靶标。总的来说，我们的结果概述了 SWH 信号传导的新功能，该功能与神经前体发育中的 caspase 依赖性非凋亡信号传导和 Wg/Wnt 信号传导相互影响，这可能与神经元发病机制有关。
The fundamental roles for the Salvador-Warts-Hippo (SWH) pathway are widely characterized in growth regulation and organ size control. However, the function of SWH pathway is less known in cell fate determination. Here we uncover a novel role of the SWH signaling pathway in determination of cell fate during neural precursor (sensory organ precursor, SOP) development. Inactivation of the SWH pathway in SOP of the wing imaginal discs affects caspase-dependent bristle patterning in an apoptosis-independent process. Such nonapoptotic functions of caspases have been implicated in inflammation, proliferation, cellular remodeling, and cell fate determination. Our data indicate an effect on the Wingless (Wg)/Wnt pathway. Previously, caspases were proposed to cleave and activate a negative regulator of Wg/Wnt signaling, Shaggy (Sgg)/GSK3 beta. Surprisingly, we found that a noncleavable form of Sgg encoded from the endogenous locus after CRISPR-Cas9 modification supported almost normal bristle patterning, indicating that Sgg might not be the main target of the caspase-dependent nonapoptotic process. Collectively, our results outline a new function of SWH signaling that crosstalks to caspase-dependent nonapoptotic signaling and Wg/Wnt signaling in neural precursor development, which might be implicated in neuronal pathogenesis.