Notch signaling controls germline stem cell niche formation in theDrosophilaovary

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.

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

“…Notch signaling can also promote stem cell maintenance indirectly; in the Drosophila ovary, the niche for the germline stem cell is created by contact with a support cell, the cap cell. Increased notch activation in the ovary leads to more cap cells, which in turn leads to more stem cells (Song et al, 2007). However, in some cases notch signaling can repress stem cell maintenance and promote differentiation.…”

“…Soluble factors such as BMPs (Xie and Spradling, 1998;Kobielak et al, 2003;Zhang et al, 2003;Andl et al, 2004;He et al, 2004;Yamashita et al, 2005), FGFs (Kashiwakura and Takahashi, 2005), Shh (Madison et al, 2005;Crosnier et al, 2006), and Wnts (Gat et al, 1998;Korinek et al, 1998;Huelsken et al, 2001;Niemann et al, 2002;Reya et al, 2003;Willert et al, 2003) are present within the niche and can originate from support cells, stem cells themselves, or differentiated cell. Cell-to-cell contact-mediated signaling is also present in adult niches in the form of connexins (Juneja et al, 1999;Plum et al, 2000), ephrins/eph (Batlle et al, 2002;Holmberg et al, 2006) and Notch (Harada et al, 1999;Lowell et al, 2000;Conboy and Rando, 2002;Calvi et al, 2003;Conboy et al, 2003;Kumano et al, 2003;Tummers and Thesleff, 2003;Hadland et al, 2004;Fre et al, 2005;Robert-Moreno et al, 2005;van Es et al, 2005;Spradling, 2006, 2007;Song et al, 2007). These signaling mechanisms may occur between stem cells, between support cells and stem cells, and between stem cells and differentiating cells.…”

Age‐related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila

“…In each germarium, GSCs are anchored to the cap cells through adherens junctions (Xie & Spradling, 2000;Song et al ., 2002). Cap cells provide the stem cell niche, as they are both necessary and sufficient for GSC self-renewal (Ward et al ., 2006;Song et al ., 2007) (Fig. 1a).…”

Régulation des cellules souches de la lignée germinale

“…Les principes qui se dégagent de l'étude des CSG chez la drosophile ont de plus été géné-ralisés à d'autres cellules souches, telles que les cellules souches hématopoïétiques ou épithéliales chez les mammifères. En effet, ces cellules souches sont ancrées à des cellules spécifiques qui émettent des signaux moléculaires identiques à ceux régulant les CSG tels que BMP, JAK-STAT, Hh ; ainsi que Wnt et Notch, qui eux n'ont pas encore été impliquées dans la régulation des CSG [45] (bien que récemment, un rôle de la voie Notch a pu être mis en évidence dans la formation de la niche [46], et en particulier dans une régulation des CSG sur le nombre de cellules composant la niche [47]). Les avantages du modèle drosophile ont donc permis de faire de rapides progrès dans l'identification et la compréhension des mécanis-mes qui contrôlent le comportement des cellules souches.…”