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Notch信号通路控制果蝇卵巢中生殖系干细胞微环境的形成。

Notch signaling controls germline stem cell niche formation in the Drosophila ovary.

作者信息

Song Xiaoqing, Call Gerald B, Kirilly Daniel, Xie Ting

机构信息

Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.

出版信息

Development. 2007 Mar;134(6):1071-80. doi: 10.1242/dev.003392. Epub 2007 Feb 7.

Abstract

Stem cells, which can self-renew and generate differentiated cells, have been shown to be controlled by surrounding microenvironments or niches in several adult tissues. However, it remains largely unknown what constitutes a functional niche and how niche formation is controlled. In the Drosophila ovary, germline stem cells (GSCs), which are adjacent to cap cells and two other cell types, have been shown to be maintained in the niche. In this study, we show that Notch signaling controls formation and maintenance of the GSC niche and that cap cells help determine the niche size in the Drosophila ovary. Expanded Notch activation causes the formation of more cap cells and bigger niches, which support more GSCs, whereas compromising Notch signaling during niche formation decreases the cap cell number and niche size and consequently the GSC number. Furthermore, the niches located away from their normal location can still sufficiently sustain GSC self-renewal by maintaining high local BMP signaling and repressing bam as in normal GSCs. Finally, loss of Notch function in adults results in rapid loss of the GSC niche, including cap cells and thus GSCs. Our results indicate that Notch signaling is important for formation and maintenance of the GSC niche, and that cap cells help determine niche size and function.

摘要

干细胞能够自我更新并产生分化细胞,在多种成体组织中,它们已被证明受周围微环境或生态位的调控。然而,构成功能性生态位的因素以及生态位形成是如何被控制的,在很大程度上仍不清楚。在果蝇卵巢中,生殖系干细胞(GSCs)与帽细胞及其他两种细胞类型相邻,已被证明是在生态位中维持的。在本研究中,我们表明Notch信号通路控制着GSC生态位的形成和维持,并且帽细胞有助于确定果蝇卵巢中生态位的大小。Notch激活的增强会导致更多帽细胞的形成和更大的生态位,从而支持更多的GSCs;而在生态位形成过程中削弱Notch信号通路则会减少帽细胞数量和生态位大小,进而减少GSC数量。此外,位于远离其正常位置的生态位,仍可通过维持高水平的局部BMP信号通路并抑制bam,像在正常GSCs中一样充分维持GSC的自我更新。最后,成体中Notch功能的丧失会导致GSC生态位迅速丧失,包括帽细胞以及因此导致GSCs的丧失。我们的结果表明,Notch信号通路对于GSC生态位的形成和维持很重要,并且帽细胞有助于确定生态位的大小和功能。

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