Wnt/β-catenin signaling within multiple cell types dependent upon kramer regulates Drosophila intestinal stem cell proliferation.
Wnt/β-catenin signaling within multiple cell types dependent upon kramer regulates Drosophila intestinal stem cell proliferation.
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多种细胞类型内的 Wnt/β-连环蛋白信号传导依赖于 kramer 调节果蝇肠干细胞增殖。
DOI：
10.1101/2023.02.21.529411
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Baskin,JeremyM
中科院分区：
文献类型：
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作者：
Sun,Hongyan;Shah,AdnanShami;Bonfini,Alessandro;Buchon,NicolasS;Baskin,JeremyM
肠上皮受持续更新的影响，这一过程依赖于Wnt/β-catenin信号驱动的肠干细胞增殖。尽管Wnt信号在ISCs中很重要，但Wnt信号在其他肠道细胞类型中的相关性以及在这些环境中调节Wnt信号的潜在机制仍然不完全清楚。利用非致命性肠道病原体对果蝇肠道的挑战，我们研究了ISC增殖的细胞决定因素，利用最近发现的Wnt信号通路调节因子kramer作为一种机械工具。我们发现Propero阳性细胞内的Wnt信号支持ISC的增殖，Kramerer通过拮抗Kelch(一种介导蓬乱的多泛素化的Cullin-3 E3连接酶适配器)来调节Wnt信号。本工作建立了Wnt/β-catenin信号在体内的生理调节因子，并提示肠内分泌细胞是一种新的细胞类型，通过Wnt/β-catenin信号调节间质干细胞的增殖。
The gut epithelium is subject to constant renewal, a process reliant upon intestinal stem cell (ISC) proliferation that is driven by Wnt/β-catenin signaling. Despite the importance of Wnt signaling within ISCs, the relevance of Wnt signaling within other gut cell types and the underlying mechanisms that modulate Wnt signaling in these contexts remain incompletely understood. Using challenge of theDrosophilamidgut with a non-lethal enteric pathogen, we examine the cellular determinants of ISC proliferation, harnessingkramer, a recently identified regulator of Wnt signaling pathways, as a mechanistic tool. We find that Wnt signaling within Prospero-positive cells supports ISC proliferation and thatkramerregulates Wnt signaling in this context by antagonizingkelch, a Cullin-3 E3 ligase adaptor that mediates Dishevelled polyubiquitination. This work establisheskrameras a physiological regulator of Wnt/β-catenin signalingin vivoand suggests enteroendocrine cells as a new cell type that regulates ISC proliferation via Wnt/β-catenin signaling.