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鉴定参与果蝇肠道干细胞调控的 O-岩藻糖基转移酶 1 的新等位基因。

Identification of a new allele of O-fucosyltransferase 1 involved in Drosophila intestinal stem cell regulation.

机构信息

College of Life Sciences, Capital Normal University, Beijing 100048, China.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

出版信息

Biol Open. 2021 Nov 15;10(11). doi: 10.1242/bio.058910. Epub 2021 Nov 3.

DOI:10.1242/bio.058910
PMID:34731235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8576262/
Abstract

Adult stem cells are critical for the maintenance of tissue homeostasis. However, how the proliferation and differentiation of intestinal stem cells (ISCs) are regulated remains not fully understood. Here, we find a mutant, stum 9-3, affecting the proliferation and differentiation of Drosophila adult ISCs in a forward genetic screen for factors regulating the proliferation and differentiation ISCs. stum 9-3 acts through the conserved Notch signaling pathway, upstream of the S2 cleavage of the Notch receptor. Interestingly, the phenotype of stum 9-3 mutant is not caused by disruption of stumble (stum), where the p-element is inserted. Detailed mapping, rescue experiments and mutant characterization show that stum 9-3 is a new allele of O-fucosyltransferase 1 (O-fut1). Our results indicate that unexpected mutants with interesting phenotype could be recovered in forward genetic screens using known p-element insertion stocks.

摘要

成体干细胞对于组织内稳态的维持至关重要。然而，肠道干细胞（ISCs）的增殖和分化是如何被调控的，目前还不完全清楚。在这里，我们在一个正向遗传筛选中发现了一个影响果蝇成体 ISC 增殖和分化的突变体，stum 9-3，该筛选的目的是寻找调控 ISC 增殖和分化的因子。stum 9-3 通过 Notch 信号通路起作用，位于 Notch 受体 S2 切割的上游。有趣的是，stum 9-3 突变体的表型不是由 stumble(stum)中断引起的，而 p-元件就插入在 stumble(stum)中。详细的定位、拯救实验和突变体特性表明，stum 9-3 是 O-岩藻糖基转移酶 1（O-fut1）的一个新等位基因。我们的结果表明，在使用已知 p-元件插入品系的正向遗传筛选中，可能会恢复具有有趣表型的意外突变体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/504ce4c2b6b3/biolopen-10-058910-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/f77062c160bd/biolopen-10-058910-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/3f3dc272bb38/biolopen-10-058910-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/130f4151ff78/biolopen-10-058910-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/504ce4c2b6b3/biolopen-10-058910-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/f77062c160bd/biolopen-10-058910-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/3f3dc272bb38/biolopen-10-058910-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/130f4151ff78/biolopen-10-058910-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1e7/8576262/504ce4c2b6b3/biolopen-10-058910-g4.jpg

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本文引用的文献

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Multifaceted regulation of Notch signaling by glycosylation.糖基化对 Notch 信号通路的多方面调控。
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The Drosophila gut: A gatekeeper and coordinator of organism fitness and physiology.果蝇肠道：机体健康和生理学的守门员和协调者。
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