E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells.

E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells.
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DOI:
10.1371/journal.pone.0012473
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发表时间:
2010-08-31
期刊:
影响因子:
3.7
通讯作者:
Yamashita YM
Yamashita YM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Inaba M;Yuan H;Salzmann V;Fuller MT;Yamashita YM

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许多成体干细胞存在于一个特殊的微环境中,称为小生境,在那里它们接收指定干细胞身份的基本信号。由钙粘蛋白和整合素介导的细胞间粘附在维持干细胞在小生境中起着至关重要的作用。在黑腹果蝇中,雄性生殖系干细胞(GSC)附着于小生境组分细胞(即,毂)。GSC中心体和纺锤体朝向中心-GSC连接,其中基于E-钙粘蛋白的粘附连接高度集中。出于这个原因,粘附连接被认为为GSC提供极性线索,以使中心体和纺锤体能够正确定向,这是迈向不对称干细胞分裂的关键一步。然而,理解E-cadherin在GSC极性中的作用一直是具有挑战性的,因为携带E-cadherin突变的GSC不能维持在小生境中。在这里,我们测试是否需要E-cadherin的GSC极性表达的显性负性形式的E-cadherin。我们发现E-cadherin确实是使GSCs向中枢细胞极化所必需的,这种作用可能由Apc 2介导。我们还证明了E-钙粘蛋白是GSC中心体定向检查点所必需的,当中心体没有正确定向时,它会阻止有丝分裂。我们提出,E-钙粘蛋白协调多个方面的干细胞的行为,包括极化的干细胞向干细胞龛界面和粘附的干细胞的龛支持细胞。
Many adult stem cells reside in a special microenvironment known as the niche, where they receive essential signals that specify stem cell identity. Cell-cell adhesion mediated by cadherin and integrin plays a crucial role in maintaining stem cells within the niche. In Drosophila melanogaster, male germline stem cells (GSCs) are attached to niche component cells (i.e., the hub) via adherens junctions. The GSC centrosomes and spindle are oriented toward the hub-GSC junction, where E-cadherin-based adherens junctions are highly concentrated. For this reason, adherens junctions are thought to provide a polarity cue for GSCs to enable proper orientation of centrosomes and spindles, a critical step toward asymmetric stem cell division. However, understanding the role of E-cadherin in GSC polarity has been challenging, since GSCs carrying E-cadherin mutations are not maintained in the niche. Here, we tested whether E-cadherin is required for GSC polarity by expressing a dominant-negative form of E-cadherin. We found that E-cadherin is indeed required for polarizing GSCs toward the hub cells, an effect that may be mediated by Apc2. We also demonstrated that E-cadherin is required for the GSC centrosome orientation checkpoint, which prevents mitosis when centrosomes are not correctly oriented. We propose that E-cadherin orchestrates multiple aspects of stem cell behavior, including polarization of stem cells toward the stem cell-niche interface and adhesion of stem cells to the niche supporting cells.
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