Drosophila models of epithelial stem cells and their niches

Abstract

Epithelial stem cells are regulated through a complex interplay of signals from diffusible ligands, cellular interactions, and attachment to the extracellular matrix. The development of Drosophila models of epithelial stem cells and their associated niche has made it possible to dissect the contribution of each of these factors in vivo, during both basal homeostasis and in response to acute damage such as infection. Studies of Drosophila epithelial stem cells have also provided insight into the mechanisms by which a healthy population of stem cells are maintained throughout adulthood by demonstrating, for example, that stem cells have a finite lifespan and may be displaced by replacement cells competing for niche occupancy. Here, we summarize the literature on each of the known Drosophila epithelial stem cells, with a focus on the two most well-characterized types, the follicle stem cells (FSCs) in the ovary and the intestinal stem cells (ISCs) in the posterior midgut. Several themes have emerged from these studies, which suggest that there may be a common set of features among niches in a variety of epithelia. For example, unlike the simpler Drosophila germline stem cell niches, both the FSC and ISC niches produce multiple, partially redundant, niche signals, some of which activate pathways such as Wnt/Wingless, Hedgehog, and epidermal growth factor (EGF) that also regulate mammalian epithelial tissue renewal. Further study into these relatively new stem cell models will be of use in understanding both the specifics of epithelial regeneration and the diversity of mechanisms that regulate adult stem cells in general.

Figure 1. The FSC niche

FSCs (light blue) reside at the region 2a/region 2b border against the basement membrane (red) and in direct contact with escort cells (green) and their immediate daughters (dark blue). It is unclear whether FSCs ever contact germ cells (pink). The germarium is surrounded by a muscle sheath (purple) that has no known role in FSC niche function. Hedgehog (Hh), Wingless (Wg), and BMP signalling are all required for FSC maintenance and the signaling ligands are produced by either the cap cells (dark pink), the escort cells, or both. It is not known whether signals from the germline or follicle cells promote FSC maintenance or regulate its activity.

Figure 2. The ISC niche

The ISCs reside throughout the posterior midgut against the basement membrane (blue) and in direct contact with enteroblasts (light green), enterocytes (yellow) and, occasionally, enteroendocrine cells (pink). The midgut is surrounded by a visceral muscle that is a key part of the ISC niche. Wingless, EGF and JAK/STAT signaling are all required for ISC maintenance and the signaling ligands are produced by several sources. During basal homeostasis, the visceral muscle produces Unpaired, Wingless and Vein, whereas diploid epithelial cells, which are probably ISCs, produce Spitz and Keren, and a few scattered enterocytes produce Unpaired 3. During infection, enterocytes increase production of JAK/STAT ligands, which act on both ISCs and the visceral muscle to increase ISC proliferation.