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对Rab GTP酶基因进行的RNA干扰筛选表明,生殖系统的体细胞在形态发生方面依赖于 ,但在干细胞微环境维持方面并非如此。 (注:原文中“reveals that somatic cells of the reproductive system depend on for morphogenesis but not stem cell niche maintenance.”部分有缺失信息,此处翻译按原文呈现)

An RNAi screen of Rab GTPase genes in reveals that somatic cells of the reproductive system depend on for morphogenesis but not stem cell niche maintenance.

作者信息

Scott Kayt, Singh Noor, Gordon Kacy Lynn

机构信息

Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599.

UNC Lineberger Comprehensive Cancer Center.

出版信息

bioRxiv. 2024 Dec 6:2024.12.03.626641. doi: 10.1101/2024.12.03.626641.

DOI:10.1101/2024.12.03.626641
PMID:39677816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11642880/
Abstract

Membrane trafficking is a crucial function of all cells and is regulated at multiple levels from vesicle formation, packaging, and localization to fusion, exocytosis, and endocytosis. Rab GTPase proteins are core regulators of eukaryotic membrane trafficking, but developmental roles of specific Rab GTPases are less well characterized, potentially because of their essentiality for basic cellular function. gonad development entails the coordination of cell growth, proliferation, and migration-processes in which membrane trafficking is known to be required. Here we take an organ-focused approach to Rab GTPase function to assess the roles of Rab genes in reproductive system development. We performed a whole-body RNAi screen of the entire Rab family in to uncover Rabs essential for gonad development. Notable gonad defects resulted from RNAi knockdown of the key regulator of ER-Golgi trafficking. We then examined the effects of tissue-specific RNAi knockdown of in somatic reproductive system and germline cells. We interrogated the dual functions of the distal tip cell (DTC) as both a leader cell of gonad organogenesis and the germline stem cell niche. We find that functions cell-autonomously and non-cell-autonomously to regulate both somatic gonad and germline development. Gonad migration, elongation, and gamete differentiation-but surprisingly not germline stem niche function-are highly sensitive to RNAi.

摘要

膜运输是所有细胞的一项关键功能,并且在从囊泡形成、包装、定位到融合、胞吐作用和内吞作用的多个层面受到调控。Rab GTPase蛋白是真核细胞膜运输的核心调节因子,但特定Rab GTPase的发育作用尚未得到充分表征,这可能是因为它们对基本细胞功能至关重要。性腺发育需要协调细胞生长、增殖和迁移过程,而这些过程已知需要膜运输。在这里,我们采用以器官为重点的方法来研究Rab GTPase的功能,以评估Rab基因在生殖系统发育中的作用。我们在[具体生物]中对整个Rab家族进行了全身RNA干扰筛选,以发现对性腺发育至关重要的Rab蛋白。内质网-高尔基体运输的关键调节因子[具体基因]的RNA干扰敲低导致了明显的性腺缺陷。然后,我们研究了在体细胞生殖系统和生殖细胞中组织特异性RNA干扰敲低[具体基因]的影响。我们探究了远端顶端细胞(DTC)作为性腺器官发生的引导细胞和生殖系干细胞微环境的双重功能。我们发现[具体基因]在细胞自主和非细胞自主水平上发挥作用,以调节体细胞性腺和生殖系的发育。性腺迁移、伸长和配子分化——但令人惊讶的是生殖系干细胞微环境功能不受影响——对[具体基因]的RNA干扰高度敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/1ab9e32f7c64/nihpp-2024.12.03.626641v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/df4e4c48c7ec/nihpp-2024.12.03.626641v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/28f2ee69d2f1/nihpp-2024.12.03.626641v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/df2ae1b14f7e/nihpp-2024.12.03.626641v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/56f340012d4a/nihpp-2024.12.03.626641v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/1ab9e32f7c64/nihpp-2024.12.03.626641v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/df4e4c48c7ec/nihpp-2024.12.03.626641v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/28f2ee69d2f1/nihpp-2024.12.03.626641v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/df2ae1b14f7e/nihpp-2024.12.03.626641v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/56f340012d4a/nihpp-2024.12.03.626641v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/11642880/1ab9e32f7c64/nihpp-2024.12.03.626641v1-f0005.jpg

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