Drosophila Quotes

Drosophila,” I said, remembering the word. “What?” Lily asked. “Why do girls always fall for guys with the at ention span of drosophila?” “What?” “Fruit flies. Guys with the attention span of fruit flies.” “Because they’re hot?” “This,” I told her, “is not the time for being truthful.

There is a reference in Aristotle to a gnat produced by larvae engendered in the slime of vinegar. This must have been Drosophila.

Why do girls always fall for guys with the attention span of drosophila?

If A was tightly linked to B, and very loosely linked to C, Sturtevant reasoned, then the three genes must be positioned on the chromosome in that order and with proportional distance from each other: A.B..........C. If an allele that created notched wings (N) tended to be co-inherited with an allele that made short bristles (SB), then the two genes, N and SB, must be on the same chromosome, while the unlinked gene for eye color must be on a different chromosome. By the end of the evening, Sturtevant had sketched the first linear genetic map of half a dozen genes along a Drosophila chromosome.

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. [...] 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.

The male fruit fly usually spots the object of his desire near the feeding area and follows her at a respectful distance until she indicates receptiveness, as a human male might send over a drink to break the ice. He then gently taps her with his foreleg. If she responds with the appropriate chemical signal, he launches into the fruit-fly courtship song, vibrating his wings in what one can only assume is the Drosophila version of Barry White. If she is sufficiently impressed with the performance to let him lick her abdomen, the deal is all but sealed, and they go on to mate. All that’s missing is the mood lighting. “I mean, talk about foreplay!” Heberlein marveled.

Drosophila has long been our main workhorse in genetics, yielding insight in the relation between chromosomes and genes.

There’s an amazing family of genes, called HOX genes. When they’re mutated in fruit flies (Drosophila melanogaster) the results are incredible phenotypes, such as legs growing out of the head14. There’s a long ncRNA known as HOTAIR, which regulates a region of genes called the HOX-D cluster. Just like the long ncRNAs investigated by Jeannie Lee, HOTAIR binds the PRC2 complex and creates a chromatin region which is marked with repressive histone modifications. But HOTAIR is not transcribed from the HOX-D position on chromosome 12. Instead it is encoded at a different cluster of genes called HOX-C on chromosome 215. No-one knows how or why HOTAIR binds at the HOX-D position. There’s a related mystery around the best studied of all long ncRNAs, Xist. Xist ncRNA spreads out along almost the entire inactive X chromosome but we really don’t know how. Chromosomes don’t normally become smothered with RNA molecules. There’s no obvious reason why Xist RNA should be able to bind like this, but we know it’s nothing to do with the sequence of the chromosome. The experiments described in the last chapter, where Xist could inactivate an entire autosome as long as it contained an X inactivation centre, showed that Xist just keeps on travelling once it’s on a chromosome. Scientists are basically still completely baffled about these fundamental characteristics of this best-studied of all ncRNAs.

Although the nucleus might have been recognized by Antonie van Leeuwenhoek in the late 17th century, it was not until 1831 that it was reported as a specific structure in orchid epidermal cells by a Scottish botanist, Robert Brown (better known for recognizing ‘Brownian movement’ of pollen grains in water). In 1879, Walther Flemming observed that the nucleus broke down into small fragments at cell division, followed by re-formation of the fragments called chromosomes to make new nuclei in the daughter cells. It was not until 1902 that Walter Sutton and Theodor Boveri independently linked chromosomes directly to mammalian inheritance. Thomas Morgan’s work with fruit flies (Drosophila) at the start of the 20th century showed specific characters positioned along the length of the chromosomes, followed by the realization by Oswald Avery in 1944 that the genetic material was DNA. Some nine years later, James Watson and Francis Crick showed the structure of DNA to be a double helix, for which they shared the Nobel Prize in 1962 with Maurice Wilkins, whose laboratory had provided the evidence that led to the discovery. Rosalind Franklin, whose X-ray diffraction images of DNA from the Wilkins lab had been the key to DNA structure, died of cancer aged 37 in 1958, and Nobel Prizes are not awarded posthumously. Watson and Crick published the classic double helix model in 1953. The final piece in the jigsaw of DNA structure was produced by Watson with the realization that the pairing of the nucleotide bases, adenine with thymine and guanine with cytosine, not only provided the rungs holding the twisting ladder of DNA together, but also provided a code for accurate replication and a template for protein assembly. Crick continued to study and elucidate the base pairing required for coding proteins, and this led to the fundamental ‘dogma’ that ‘DNA makes RNA and RNA makes protein’. The discovery of DNA structure marked an enormous advance in biology, probably the most significant since Darwin’s publication of On the Origin of Species .

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?

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.

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.