Signaling in stem cell niches: lessons from theDrosophilagermline

Abstract

Stem cells are cells that, upon division, can produce new stem cells as well as daughter cells that initiate differentiation along a specific lineage. Studies using the Drosophila germline as a model system have demonstrated that signaling from the stem cell niche plays a crucial role in controlling stem cell behavior. Surrounding support cells secrete growth factors that activate signaling within adjacent stem cells to specify stem cell self-renewal and block differentiation. In addition, cell-cell adhesion between stem cells and surrounding support cells is important for holding stem cells close to self-renewal signals. Furthermore, a combination of localized signaling and autonomously acting proteins might polarize stem cells in such a way as to ensure asymmetric stem cell divisions. Recent results describing stem cell niches in other adult stem cells, including hematopoietic and neural stem cells, have demonstrated that the features characteristic of stem cell niches in Drosophila gonads might be conserved.

Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis

“…In addition to maintaining stem cell identity, other significant biological activities that are shared by Wnts and Cripto-1 are their ability to stimulate cell motility, invasion and EMT, as previously discussed in this review Bianco et al, 2003;Kemler et al, 2004;Strizzi et al, 2004;Endo et al, 2005;Yook et al, 2005). Loss of cell-cell adhesion due to a reduction in E-cadherin expression, possibly through Wnt/Cripto-1 crosstalk, may also affect the integrity of the stem cell niche since cell adhesion between supporting niche cells and stem cells is required for stem cell survival and asymmetric cell division (Matsui and Okamura, 2005;Yamashita et al, 2005). Reciprocally, a loss of cell-cell adhesion due to a repression of E-cadherin expression may also be important for the movement of differentiated intestinal and skin epithelial cells from the niche as occurs in the intestinal crypts and in the bulge region of the papillae of the hair follicles.…”

Regulation of apoptosis in Drosophila

“…13 Significantly, the Wnt pathway has been implicated in regulating self-renewal of stem cells and tissue regeneration, both in vertebrates and insects. [69][70][71][72] Therefore, it is possible that a similar mechanism operates in vertebrates. Also, mitogenic signaling by doomed cells may contribute to the formation of neoplastic tumors.…”

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

“…They may regulate survival, cell cycle kinetics, cell proliferation, and differentiation. A key role of the BMPs was initially identified in the Drosophila ovary, where the BMP homologue decapentaplegic (dpp) secreted by neighboring cells maintains the germinal stem cell state (Xie and Spradling, 1998;Yamashita et al, 2005). BMPs have diverse roles in several mammalian stem cell niches.…”

“…A wide range of instructive signals can, therefore, regulate stem cell behavior. 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).…”