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肌球蛋白介导的顶端收缩促进了秀丽隐杆线虫中生理生殖细胞的死亡。

Actomyosin-mediated apical constriction promotes physiological germ cell death in C. elegans.

机构信息

Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland.

Molecular Life Science PhD Program, University of Zürich and ETH Zürich, Zürich, Switzerland.

出版信息

PLoS Biol. 2024 Aug 23;22(8):e3002775. doi: 10.1371/journal.pbio.3002775. eCollection 2024 Aug.

DOI:10.1371/journal.pbio.3002775
PMID:39178318
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11376560/
Abstract

Germ cell apoptosis in Caenorhabditis elegans hermaphrodites is a physiological process eliminating around 60% of all cells in meiotic prophase to maintain tissue homeostasis. In contrast to programmed cell death in the C. elegans soma, the selection of germ cells undergoing apoptosis is stochastic. By live-tracking individual germ cells at the pachytene stage, we found that germ cells smaller than their neighbors are selectively eliminated through apoptosis before differentiating into oocytes. Thus, cell size is a strong predictor of physiological germ cell death. The RAS/MAPK and ECT/RHO/ROCK pathways together regulate germ cell size by controlling actomyosin constriction at the apical rachis bridges, which are cellular openings connecting the syncytial germ cells to a shared cytoplasmic core. Enhancing apical constriction reduces germ cell size and increases the rate of cell death while inhibiting the actomyosin network in the germ cells prevents their death. We propose that actomyosin contractility at the rachis bridges of the syncytial germ cells amplifies intrinsic disparities in cell size. Through this mechanism, the animals can adjust the balance between physiological germ cell death and oocyte differentiation.

摘要

秀丽隐杆线虫雌雄同体生殖细胞凋亡是一个生理过程,可清除减数分裂前期约 60%的所有细胞,以维持组织内稳态。与线虫体细胞的程序性细胞死亡不同,发生凋亡的生殖细胞的选择是随机的。通过在粗线期对单个生殖细胞进行实时追踪,我们发现,在分化为卵母细胞之前,比其相邻细胞小的生殖细胞通过凋亡被选择性清除。因此,细胞大小是生理生殖细胞死亡的一个强有力的预测指标。RAS/MAPK 和 ECT/RHO/ROCK 途径通过控制连接合胞体生殖细胞和共享细胞质核心的顶端脊索桥的肌动球蛋白收缩来共同调节生殖细胞大小,脊索桥是连接合胞体生殖细胞的细胞开口。增强顶端收缩会减小生殖细胞的大小并增加细胞死亡的速度,而抑制生殖细胞中的肌动球蛋白网络则可以防止它们死亡。我们提出,合胞体生殖细胞脊索桥上的肌动球蛋白收缩放大了细胞大小的内在差异。通过这种机制,动物可以在生理生殖细胞死亡和卵母细胞分化之间调整平衡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/b65a6e7eddaa/pbio.3002775.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/9b32ec0143e7/pbio.3002775.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/e1c51e48db0b/pbio.3002775.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/11e76b57895f/pbio.3002775.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/d153d36d96b5/pbio.3002775.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/95662699dd01/pbio.3002775.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/4764458bf9a9/pbio.3002775.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/b65a6e7eddaa/pbio.3002775.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/9b32ec0143e7/pbio.3002775.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/e1c51e48db0b/pbio.3002775.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/11e76b57895f/pbio.3002775.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/d153d36d96b5/pbio.3002775.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/95662699dd01/pbio.3002775.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/4764458bf9a9/pbio.3002775.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c254/11376560/b65a6e7eddaa/pbio.3002775.g007.jpg

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本文引用的文献

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A hydraulic instability drives the cell death decision in the nematode germline.一种水力不稳定性驱动线虫生殖系中的细胞死亡决定。
Nat Phys. 2021;17(8):920-925. doi: 10.1038/s41567-021-01235-x. Epub 2021 May 20.
2
Non-autonomous regulation of germline stem cell proliferation by somatic MPK-1/MAPK activity in C. elegans.线虫体细胞 MPK-1/MAPK 活性对生殖干细胞增殖的非自主调控。
Cell Rep. 2021 May 25;35(8):109162. doi: 10.1016/j.celrep.2021.109162.
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Tissue-specific regulation of epidermal contraction during Caenorhabditis elegans embryonic morphogenesis.
秀丽隐杆线虫胚胎形态发生过程中表皮收缩的组织特异性调节。
G3 (Bethesda). 2021 Jul 14;11(7). doi: 10.1093/g3journal/jkab164.
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Rocking the Boat: The Decisive Roles of Rho Kinases During Oocyte, Blastocyst, and Stem Cell Development.扰乱平衡:Rho激酶在卵母细胞、囊胚和干细胞发育过程中的决定性作用
Front Cell Dev Biol. 2021 Jan 11;8:616762. doi: 10.3389/fcell.2020.616762. eCollection 2020.
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Cellpose: a generalist algorithm for cellular segmentation.Cellpose:一种通用的细胞分割算法。
Nat Methods. 2021 Jan;18(1):100-106. doi: 10.1038/s41592-020-01018-x. Epub 2020 Dec 14.
6
ERK phosphorylates chromosomal axis component HORMA domain protein HTP-1 to regulate oocyte numbers.ERK 磷酸化染色质轴组件 HORMA 域蛋白 HTP-1 以调节卵母细胞数量。
Sci Adv. 2020 Oct 30;6(44). doi: 10.1126/sciadv.abc5580. Print 2020 Oct.
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PIG-1 MELK-dependent phosphorylation of nonmuscle myosin II promotes apoptosis through CES-1 Snail partitioning.PIG-1 依赖于 MELK 的磷酸化作用促进非肌肉肌球蛋白 II 的凋亡,通过 CES-1 将 Snail 进行分区。
PLoS Genet. 2020 Sep 18;16(9):e1008912. doi: 10.1371/journal.pgen.1008912. eCollection 2020 Sep.
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Construction of a germline-specific RNAi tool in C. elegans.在秀丽隐杆线虫中构建生殖系特异性 RNAi 工具。
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9
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10
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