Drosophila male and female germline stem cell niches require the nuclear lamina protein Otefin.
Drosophila male and female germline stem cell niches require the nuclear lamina protein Otefin.
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DOI：
10.1016/j.ydbio.2016.05.001
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发表时间：
2016-07-01
影响因子：
2.7
通讯作者：
Geyer PK
中科院分区：
文献类型：
--
作者：
Barton LJ;Lovander KE;Pinto BS;Geyer PK
核层是位于内核被膜之下的广泛的蛋白质网络。该网络包括 LAP2-emerin-MAN1 结构域 (LEM-D) 蛋白家族，这些蛋白与染色质结合蛋白自整合屏障因子 (BAF) 具有关联性。单个 LEM-D 蛋白的缺失会导致进行性组织限制性疾病，称为核纤层蛋白病。与核纤层蛋白病相关的机制尚不清楚。在这里，我们介绍了对果蝇核层 LEM-D 蛋白之一 Otefin (Ote) 的研究，Otefin (Ote) 是 emerin 的同源物。先前的研究表明，Ote 是雌性生殖干细胞 (GSC) 存活所必需的。我们证明 Ote 也是卵巢微环境中体细胞存活所必需的，Ote 的缺失会导致帽细胞数量减少和信号转导改变。我们发现 Ote 的生殖细胞限制性表达可以挽救这些缺陷，揭示 Ote 在生态位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，我们还研究了 Ote 对男性生育力的需求。我们发现，随着年龄的增长，ote−/− 雄性会过早不育。与在雌性中的观察结果相似，这种不育性与 GSC 损失和生态位体细胞的变化有关，这些表型很大程度上是通过生殖细胞限制的 Ote 表达来挽救的。综上所述，我们的研究表明，Ote 是两个干细胞群自主生存所必需的，也是非自主维持两个体细胞生态位所必需的。最后，我们的数据进一步证明 LEM-D 蛋白在干细胞存活和组织稳态中发挥着关键作用。
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.