Emerin通过维持中心体和核薄层结构来维持干细胞的存活。

IF 3.7 2区 生物学 Q1 DEVELOPMENTAL BIOLOGY Development Pub Date : 2024-11-15 Epub Date: 2024-11-13 DOI:10.1242/dev.204219
Samuel D Jones, Jack E B Miller, Madilynn M Amos, Julianna M Hernández, Katherine M Piaszynski, Pamela K Geyer
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引用次数: 0

摘要

果蝇雌性生殖干细胞(GSC)在完整但可渗透的核包膜和核薄层(NL)存在下完成不对称有丝分裂。这种不对称分裂需要经过修饰的中心体循环,其中有丝分裂期中心体带着成熟的核周物质(PCM)嵌入核层,而间期中心体带着减少的 PCM 离开核层。这种中心体循环需要emerin,这是一种对GSC存活和生殖细胞分化至关重要的NL蛋白。在emerin突变体中,间期GSC的中心体保留过多的PCM,继续嵌入NL,并在NL扭曲的位置核化微管星。在这里,我们探讨了异常的间期中心体对 GSC 丧失的贡献。值得注意的是,减少emerin突变体中的间期PCM可以挽救GSC的存活并部分恢复生殖细胞分化。通过表达组成型活性波罗激酶直接测试了异常中心体的影响,该激酶能促使野生型GSC的间期中心体增大。值得注意的是,这些条件未能改变 NL 结构或降低 GSC 的存活率。然而,将增大的间期中心体与核变形结合起来会促进GSC的丧失。这些研究证实,emerin能维持中心体结构,从而保持干细胞存活。
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Emerin preserves stem cell survival through maintenance of centrosome and nuclear lamina structure.

Drosophila female germline stem cells (GSCs) complete asymmetric mitosis in the presence of an intact, but permeable, nuclear envelope and nuclear lamina (NL). This asymmetric division requires a modified centrosome cycle, wherein mitotic centrosomes with mature pericentriolar material (PCM) embed in the NL and interphase centrosomes with reduced PCM leave the NL. This centrosome cycle requires Emerin, an NL protein required for GSC survival and germ cell differentiation. In emerin mutants, interphase GSC centrosomes retain excess PCM, remain embedded in the NL and nucleate microtubule asters at positions of NL distortion. Here, we investigate the contributions of abnormal interphase centrosomes to GSC loss. Remarkably, reducing interphase PCM in emerin mutants rescues GSC survival and partially restores germ cell differentiation. Direct tests of the effects of abnormal centrosomes were achieved by expression of constitutively active Polo kinase to drive enlargement of interphase centrosomes in wild-type GSCs. Notably, these conditions failed to alter NL structure or decrease GSC survival. However, coupling enlarged interphase centrosomes with nuclear distortion promoted GSC loss. These studies establish that Emerin maintains centrosome structure to preserve stem cell survival.

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来源期刊
Development
Development 生物-发育生物学
CiteScore
6.70
自引率
4.30%
发文量
433
审稿时长
3 months
期刊介绍: Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community. Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication. To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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