Basolateral junction proteins regulate competition for the follicle stem cell niche in the Drosophila ovary.

Basolateral junction proteins regulate competition for the follicle stem cell niche in the Drosophila ovary.
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DOI:
10.1371/journal.pone.0101085
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Nystul TG
Nystul TG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kronen MR;Schoenfelder KP;Klein AM;Nystul TG

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上皮干细胞在成年期通常会丢失或受损,因此必须更换以维持体内平衡。最近的研究表明,在许多类型的上皮组织中,干细胞替代通过中性竞争发生,但对决定竞争结果的因素知之甚少。果蝇卵巢中的上皮卵泡干细胞(FSC)在正常的稳态过程中经常丢失和更换,我们发现FSC更换符合中性竞争模型。此外,我们发现,FSC突变体的基底外侧连接基因,致命的巨大幼虫(lgl)或光盘大(dlg),经历了一个偏向的竞争,其特征在于增加入侵邻近FSC和减少损失的生态位占用。有趣的是,第三基底外侧连接基因scribble(scribb)的FSC突变体不表现出有偏向的竞争,表明Lgl和Dlg通过Scrib-independent过程调节生态位竞争。最后,我们发现FSC具有独特的细胞极性,其特征在于广泛分布的粘附连接和缺乏成熟的顶端结构域。总的来说,这些观察结果表明,Lgl和Dlg促进FSC后代分化到它们不太倾向于侵入相邻生态位的状态。此外,我们证明了中性漂移模型可以适用于量化突变克隆的非中性行为。
Epithelial stem cells are routinely lost or damaged during adult life and must therefore be replaced to maintain homeostasis. Recent studies indicate that stem cell replacement occurs through neutral competition in many types of epithelial tissues, but little is known about the factors that determine competitive outcome. The epithelial follicle stem cells (FSCs) in the Drosophila ovary are regularly lost and replaced during normal homeostasis, and we show that FSC replacement conforms to a model of neutral competition. In addition, we found that FSCs mutant for the basolateral junction genes, lethal giant larvae (lgl) or discs large (dlg), undergo a biased competition for niche occupancy characterized by increased invasion of neighboring FSCs and reduced loss. Interestingly, FSCs mutant for a third basolateral junction gene, scribble (scrib), do not exhibit biased competition, suggesting that Lgl and Dlg regulate niche competition through a Scrib-independent process. Lastly, we found that FSCs have a unique cell polarity characterized by broadly distributed adherens junctions and the lack of a mature apical domain. Collectively, these observations indicate that Lgl and Dlg promote the differentiation of FSC progeny to a state in which they are less prone to invade the neighboring niche. In addition, we demonstrate that the neutral drift model can be adapted to quantify non-neutral behavior of mutant clones.
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