P52. The role of heparan sulfate proteoglycans in Drosophila germline stem cell niche

Stem cell posses the remarkable characteristics to produce its daughter cell that retain a stem-cell identity and the other that differentiates. Stem cells reside in dedicated cellular microenvironments termed stem-cell niches. These niches dictate a stem-cell identity, maintain the stem cell population, and coordinate proper homeostatic production of differentiated cells. Drosophila germ line stem cells (GSCs) are one of the ideal models for stem cell study in vivo . In apical tips of both male and female gonads, GSCs associate with specially differentiated somatic gonadal cells, the niche cells. These niche cells generate niches for GSCs by secreting signaling molecules, such as TGF-beta ligand, Dpp and JAK/STAT ligand Upd, which are essential for GSC maintenance. Although these facts indicate that region of niche is defined by the spatial distribution of these ligands, molecular mechanisms that regulate ligand distribution within the niche is not characterized. Heparan sulfate proteoglycans (HSPGs) are one kind of glycoprotein which are expressed on the cell surface and/or in the extracellular matrix. Recent in vivo studies have shown that HSPGs play critical roles in regulating signaling during development by a variety of mechanisms including regulation of extracellular ligand distribution. Here we show that Drosophila HSPGs are essential components of GSC niche. Drosophila two glypians, a subfamily of HSPGs, dally and dally-like were expressed in niche cells of female and male gonads, respectively and were required for GSC maintenance. In GSCs of these glypican mutants, signaling which is essential for GSC maintenance were impaired. Conversely, when dally was ectopically expressed in ovaries, we observed expansion of GSC niche. These results showed that these glypicans define niche region by regulating range of niche signal activity, presumably by controlling ligand distribution. HSPGs are evolutionally conserved molecules, thus our results imply HSPGs are general niche components that define niche region molecularly.