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First in Fly: Drosophila Research and Biological Discovery First in Fly: Drosophila Research and Biological Discovery by Stephanie Elizabeth Mohr
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“What would fly researchers discover at the tips of the reproductive structures? In the immediate environment in which the GSC (germline stem cells) sit? Shangri-La.
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The experimental biologist J.J. Trentin proposed in 1970 that within the bone marrow and other home locations, there exists 'hematopoietic inductice microenvironment' with the unique ability to serve as a home location for blood stem cells. In the later 1970s, another blood cell expert, R. Schofield, referred to this specialized microenvironment as a 'niche', introducing the term that would stick and eventually, become widely applied to describe the microenvironment surrounding any type of stem cell. Fly biologist H. Lin describes a stem cell niche as 'the Shangri-La, the idyllic hideaway' in which these cells reside. Nestled in the niche, Lin states, stem cells 'thrive to self-renew and to produce numerous daughter cells that will differentiate and age as they leave the paradise'. In other words, the niche is the place that a stem cell is granted its two wishes - allowing it both to remain and to become something else.”
Stephanie Elizabeth Mohr, First in Fly: Drosophila Research and Biological Discovery
“Another area of interest is to explore what happens to stem cells and tissue homeostasis - to the maintenance process - as we age. In studies reported in 2011 and 2012, M. Rera, D.W. Walker, and colleagues added blue dye to fly food and then asked whether that blue color is restricted to the simple tube of the gut running through the adult, as is visible in the translucent belly of the fly, or whether the dye turns the whole fly blue, indicating that the gut has become permeable. This assay, known as the Smurf assay, gives a quick, high-level indication of gut damage that can be followed by more detailed analyses such as detection of stem cell division and signal tranduction pathway activity in dissected fly guts, or electron micrograph imaging of the mucus layer that separates the food from the gut cells. An increased prevalence of gut permeability turns out to be associated with aging in flies, and might be one of a cluster of events associated with a late-in-life 'death spiral'. Moreover, 'Smurfing' (turning blue in the assay) has been observed not only following direct perturbation of the fly gut but also among flies subjected to brain trauma, suggesting that gut permeability might be a general hallmark of impending death. The smurf assay - which requires no fancy equipment, no dissection, no costly reagents - has since been used in studies of two other Drosophilia species (D. mojavensis and D. virilis), as well in worms and zebrafish. New assays allow us to ask new questions; the answers to those questions lead us forward to the next.”
Stephanie Elizabeth Mohr, First in Fly: Drosophila Research and Biological Discovery
“The study of stem cell niches in mammalian systems presents an 'arduous endeavor'; in comparison, the fly germarium is relatively easy to manipulate. In the 1990s, H. Lin, A.C. Spradling, and others used of a number of approaches to study Drosophilia GSCs and their niche, including killing specific cells in the germarium with precisely directed lasers; transplantation of cells from the ovary of one fly to another; and genetic perturbations that included the dialing up or down of Hh pathway signaling. The researchers found that following laser ablation of cells surrounding the GSCs - that is killing the niche cells - all the GSCs went on to form eggs, and the system was quickly depleted of its GSC reserve. Moreover, through genetic analyses the researchers identified specific genes required in the niche cells to maintain GSCs within the niche, as would be deduced for a gene that, when disrupted in niche cells, has the same effect as laser ablation of those cells. These studies are credited with providing the first clear experimental evidence of a stem cell niche, as well as defining what genes - what signaling pathways and other cellular activities - are important to the process. Many of the same pathways relevant in other cell types proved relevant to communication between the niche and GSCs, including the Hh pathway. The genes required for suppression of transposon mobilization by the piRNA system also have relevance to the GSC niche; disruption of the piwi gene, for example, can lead to uncontrolled proliferation of GSCs.”
Stephanie Elizabeth Mohr, First in Fly: Drosophila Research and Biological Discovery
“Though the Drosophilia ovary is a structure with a different purpose - one designed to make fly eggs, not blood cells - the ovary, and specifically, the substructure of the ovary known as the 'germarium', have similarities with what was described for hematopoiesis. The organization of the cells that make up the germarium can be likened to a knitted winter hat pulled over the wearer's head. The extreme end - the pompon - comprises a set of cells called the 'terminal filament' cells; the top of the hat is formed by anterior 'cap' cells; and the sides of the hat are made up of more lateral 'inner sheath' cells that surround the GSCs themselves. Within this small cluster of cells, precise positions matter. When a GSC divides in two, one cell remains in contact with the cap cells and the other loses this immediate proximity. The cell that remains in contact with cap cells remains a GSC. The more posterior-positioned cell, by contrast, goes on to form an egg. A similar setup exists in the Drosophilia testes, in which 'hub' cells sit immediately anterior to the male GSCs. A question arises, what is special about the proximity of a GSC to a cap cell that keeps one daughter of a recently divided stem a stem cell while its sister goes on to form an egg?”
Stephanie Elizabeth Mohr, First in Fly: Drosophila Research and Biological Discovery