An empty Drosophila stem cell niche reactivates the proliferation of ectopic cells

Abstract

Stem cells are thought to reside in regulatory microenvironments (“niches”) generated by stable stromal neighbors. To investigate the significance of empty niches vacated by stem cell loss, we studied Drosophila ovarioles, which maintain two to three germ-line stem cells in a niche requiring adhesive stromal cap cells and Decapentaplegic signals. After experimentally emptying the germ-line stem cell niche, cap cell activity persists for several weeks. Initially, somatic inner germarium sheath cells enter the empty niche, respond to Dpp, but fail to divide. Subsequently, follicle cell progenitors, including somatic stem cells enter the niche, respond to Dpp, and proliferate as long as cap cells remain. Proliferation requires the normal hedgehog signal of the somatic stem cells as well as proximity to the niche. Thus, empty niches can persist, signal incoming cells, and support ectopic proliferation. Similar events may underlie some disease states

Genetic dissection of a stem cell niche: The case of the Drosophila ovary

“…The formation of GSC tumors in response to bab1-Gal4-driven expression of dpp in anterior somatic cells, the likely source of BMP ligands in the GSC niche, suggests that the levels of BMP/Dpp ligand are an essential limiting factor in the normal restriction of GSC maintenance to those cells in contact with the CpC cells. In this regard, we note that dpp expression primarily from somatic cells within region 2 of the germaria also induces similar GSC tumors (Kai and Spradling, 2003;Zhu and Xie, 2003;Song et al, 2004), suggesting that GSC tumor phenotypes are sensitive to the availability, but not to the pattern, of ligand expression within the germarium.…”

“…2C), we thought that bab1-Gal4 might be useful for the ectopic expression of ligands in the stromal CpCs, TFCs, and IGS cells. To test this, we wanted to determine if bab1-Gal4-mediated expression of dpp could induce hyperplastic GSC growth, characterized by the presence of hundreds of spherical spectrosome containing GSC-like cells, which has previously been observed when dpp was expressed in FCs and IGS cells (Kai and Spradling, 2003;Zhu and Xie, 2003;Song et al, 2004;Xi et al, 2005). However, we found that ectopic expression of dpp when driven by bab1-Gal4 was lethal (data not shown).…”

“…In the wildtype situation, BMP pathway activation in the germline is restricted to only GSCs in contact with CpCs plus occasional "pre-CBs" (Kai and Spradling, 2003;Casanueva and Ferguson, 2004;Song et al, 2004). The formation of GSC tumors in response to bab1-Gal4-driven expression of dpp in anterior somatic cells, the likely source of BMP ligands in the GSC niche, suggests that the levels of BMP/Dpp ligand are an essential limiting factor in the normal restriction of GSC maintenance to those cells in contact with the CpC cells.…”

“…Upon ligand binding, these receptors act to phosphorylate Mad, a Smad transcription factor, which in conjunction with other proteins acts to regulate the expression of target genes. In the adult GSC niche, only the 2-3 anterior germ cells in contact with CpCs possess high levels of BMP pathway activity (phosphorylated Mad protein) (Kai and Spradling, 2003). BMP ligands Dpp (encoded by decapentaplegic) and Gbb (encoded by glass-bottomed boat) are required for GSC maintenance in both Drosophila ovaries and testis (Wong et al, 2005).…”

Niche regulation of corneal epithelial stem cells at the limbus

“…The latter hypothetical scenario, if proven, illustrates an exciting new possibility for the limbal niche in directing trafficking and homing of host circulating SCs, an emerging concept well documented in the hematopoietic niche (for review, see [102]), and the Drosophila germline niche [103].…”