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Drosophila male and female germline stem cell niches require the nuclear lamina protein Otefin

机译:果蝇雄性和雌性种系干细胞生态位需要核层蛋白Otefin。

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摘要

The nuclear lamina is an extensive protein network that underlies the inner nuclear envelope. This network includes the LAP2-emerin-MAN1-domain (LEM-D) protein family, proteins that share an association with the chromatin binding protein Barrier-to-autointegration factor (BAF). Loss of individual LEM-D proteins causes progressive, tissue-restricted diseases, known as laminopathies. Mechanisms associated with laminopathies are not yet understood. Here we present our studies of one of the Drosophila nuclear lamina LEM-D proteins, Otefin (Ote), a homologue of emerin. Previous studies have shown that Ote is autonomously required for the survival of female germline stem cells (GSCs). We demonstrate that Ote is also required for survival of somatic cells in the ovarian niche, with loss of Ote causing a decrease in cap cell number and altered signal transduction. We show germ cell-restricted expression of Ote rescues these defects, revealing a non-autonomous function for Ote in niche maintenance and emphasizing that GSCs contribute to the maintenance of their own niches. Further, we investigate the requirement of Ote in the male fertility. We show that ote−/− males become prematurely sterile as they age. Parallel to observations in females, this sterility is associated with GSC loss and changes in somatic cells of the niche, phenotypes that are largely rescued by germ cell-restricted Ote expression. Taken together, our studies demonstrate that Ote is required autonomously for survival of two stem cell populations, as well as non-autonomously for maintenance of two somatic niches. Finally, our data add to growing evidence that LEM-D proteins have critical roles in stem cell survival and tissue homeostasis.
机译:核层是广泛的蛋白质网络,是内部核膜的基础。该网络包括LAP2-emerin-MAN1域(LEM-D)蛋白质家族,这些蛋白质与染色质结合蛋白Barrier-to-autointegration factor(BAF)共享关联。单个LEM-D蛋白的丢失会导致进行性,组织受限的疾病,称为拉丁病。尚不清楚与laminopathies相关的机制。在这里,我们介绍我们对果蝇核纤层LEM-D蛋白之一Otefin(Ote)(一种Emerin的同源物)的研究。先前的研究表明,雌性种系干细胞(GSC)的生存需要Ote。我们证明Ote是卵巢小生境中体细胞存活所必需的,Ote的丢失导致帽细胞数减少和信号转导改变。我们显示Ote的生殖细胞限制表达挽救了这些缺陷,揭示了Ote在利基维持中的非自主功能,并强调GSC有助于维持其自身的生态位。此外,我们调查了男性生育中Ote的需求。我们显示,随着年龄的增长,ote -/-男性变得过早不育。与雌性观察平行的是,这种不育与GSC的丧失和利基体细胞的变化有关,这些表型在很大程度上受生殖细胞限制的Ote表达所挽救。两者合计,我们的研究表明Ote是两个干细胞群体生存的自主需要,并且非自治地需要维持两个体细胞小生境。最后,我们的数据增加了越来越多的证据,表明LEM-D蛋白在干细胞存活和组织稳态中具有关键作用。

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