why do we study drosophila melanogaster

The fruit fly, Drosophila melanogaster

, is used as a model organism to study disciplines ranging from fundamental genetics to the development of tissues and organs. Drosophila genome is 60% homologous to that of humans, less redundant, and about 75% of the genes responsible for human diseases have homologs in flies (Ugur et al., 2016).

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How do flies control cancer?

The mechanisms controlling cancer immune response are somehow conserved also in flies as studies in Drosophila have shown that infiltration of macrophages (called hemocytes) in cancer cells requires the activation of the JAK-STAT, JNK, TNF-α, and Toll/Imd/TLR signaling pathways (Bangi, 2013 ). Of particular interest is TNF-α that plays an important role in controlling apoptosis and the inflammation processes (Ham et al., 2016 ). TNF-α in tumors has distinct and overlapping functions to promote tumor growth and proliferation and to activate cell death, functions that are mainly mediated by the activation of TNFR1 that is ubiquitously expressed while TNFR2, mainly expressed in immune cells, is less well understood. Thus these opposite signaling pathways activated by TNF signals depend on the adaptor complexes recruited by the receptors and by the cellular context, and they may create a problem for the development of therapeutic strategies that target TNF signaling in tumors (Ham et al., 2016 ). In Drosophila the sole TNF-α, called Eiger (Egr), binds two receptors called Wengen (Kanda et al., 2002) and Grindelwald (Andersen et al., 2015 ), the latter shown necessary for the growth of RasV12/scribble−/− tumors (Andersen et al., 2015 ). An interesting mechanism links the possibility that ROS, induced by stress or local inflammation, triggers Egr expression in the hemocytes, to control JNK signaling, in a phenomenon called Apoptosis-Induced Proliferation (AIP), a sort of compensatory proliferative response of the epithelial cells that responds to cues from local “activated” hemocytes (Fogarty et al., 2016 ). Other studies highlighted the role of hemocytes in the interplay between inflammation and cancer, i.e., using a classic cancer model that recapitulates the hallmarks of epithelial cancer cells ( Rasv12 / scribble−/− ), it was shown that cancer cells induce hemocyte's recruitment and proliferation in vivo by activating JNK signaling to cause the expression of JAK/STAT cytokines (Pastor-Pareja et al., 2008 ). Using a similar model it was shown that Egr expression was higher in the hemocytes derived from cancer animals, and that its activity was necessary to stimulate invasive migration of tumor cells (Cordero et al., 2010 ). On the contrary, Egr acts as a tumor suppressor to drive apoptosis in cancer cells upon activation of Toll/NF-κB signaling by the fat body (adipocytes) in response to the secretion of Egr by the circulating “activated” hemocytes (Parisi et al., 2014 ). Work using allograft transplantation experiments, identify also a function for the hemocytes in tumor initiation, that is independent on Eiger, but relays rather on the activation by external stimuli (i.e., CIN, abnormal growth) of JNK pathway and on the complex of non-autonomous and autonomous signals between tumor cells and those composing the tumor microenvironment; a similar mechanism has been proposed in vertebrates suggesting a conserved response for JNK signaling in fly to control initial tumor growth (Muzzopappa et al., 2017 ).

What is the SWH pathway?

The Salvador-Warts-Hippo (SWH) tumor suppressor pathway was discovered first in Drosophila as a regulator of organ size (Pan, 2010; Yu et al., 2015) and later in humans, where it was found to be fundamental in the regulation of cancer growth (Harvey et al., 2013 ). The physiological activation of the Hippo (HPO) kinase, (MST1/2 in human) (Harvey et al., 2003) consists in the phosphorylation of Warts (WTS), (LATS1/2 in human) (Genevet et al., 2010; Yu et al., 2010) and in the activation of the phosphorylated core complex, that includes Salvador (SAV in human) (Tapon et al., 2002) and Mob/MATS, that in turn, phosphorylate Yki (YAP/TAZ in humans) (Oh and Irvine, 2008 ). Phosphorylated Yki is sequestered and degraded in the cytoplasm, resulting in the inhibition of its nuclear transcriptional activity and oncogenic function (Harvey et al., 2013 ). Upstream, the Hippo cascade is regulated by components of cell junctions, including cell adhesion molecules such as Merlin, a homolog of the human Neurofibromatosis Type 2 (NF2) (Genevet et al., 2010; Yu et al., 2010 ), which acts as tumor suppressor; the cadherin Fat in complex with Dachsous; and by cell polarity regulators such as Crumbs (Robinson et al., 2010; Harvey et al., 2013 ). Alterations in the composition of the core proteins (HPO, WTS, SAV, MATS) of the pathway trigger Yki translocation into the nucleus that binds tissue-specific partners and induces the expression of its target genes, among them: CyclinE, dIAP1 and MYC (Harvey et al., 2003; Pantalacci et al., 2003; Neto-Silva et al., 2010; Ziosi et al., 2010 ). This articulated system is also tightly regulated by other signaling pathways: for example, in the Drosophila imaginal wing disc, Lgl or aPKC deregulation results in JNK activation to promote Yki nuclear translocation via phosphorylation of Ajuba (Jub), an upstream regulator of the cascade that binds to and inhibits Wts kinase activity (Sun and Irvine, 2013 ). In addition to the regulation of cell-cell interaction signals, components of the Hippo pathway have been found to be sensitive to mechanical stress (Panciera et al., 2017 ). This mechanotransduction function is critical in the control of physiological pathways, and its deregulation may contribute to the abnormal cell behavior in diseases such as cancer, where the cells in the tumor have to sustain physical forces generated by tissue overgrowth. Interestingly, this last function has shown differences in the behavior of Yki between human and flies: indeed, in Drosophila the Yki protein does not respond to integrin stimulation, while in mammals integrin signaling promotes YAP/TAZ activity. One possible explanation for this different behavior may be that the N-terminus of Yki is missing a domain necessary to bind PDZ-containing proteins, which is found in its human counterpart YAP, and is necessary for the activation of the integrin-Src adhesion branch of the pathway (Elbediwy and Thompson, 2018 ). However, an interesting and potential explanation for this difference comes from a comparative analysis of the Yki protein and the evolution of the different epithelia: this analysis outlines how in Drosophila the apical membrane of the columnar epithelium is well differentiated in its function to activate the Hippo pathway, whereas in mammals the multilayer of cells lacks a functional apical domain, and the activation of YAP/TAZ relies on the activation/signal from the integrin adhesion pathways of the stem cells on the basal layer of the epithelium (Elbediwy and Thompson, 2018 ).

What is Drosophila used for?

Recently, Drosophila was also used to generate multigenic models of colon cancer using data from patients from The Cancer Genome Atlas. Interestingly, the outcomes of these models mimicked important properties of human cancers, and can be explored and used in chemical screens to find new combinations of cancer-relevant drugs (Bangi et al., 2016 ). Studies, using Drosophila models, to characterize intestinal human pathophysiology, revealed the high conservation between these species of the mechanisms underlaying colorectal tumorigenesis (Christofi and Apidianakis, 2013 ), and further revealed also the mechanisms that control the processes leading to bacterial-mediated inflammation (Lemaitre and Hoffmann, 2007 ).

How do fruit fly models help to study cancer?

Cancer is a multistep disease driven by the activation of specific oncogenic pathways concomitantly with the loss of function of tumor suppressor genes that act as sentinels to control physiological growth. The conservation of most of these signaling pathways in Drosophila, and the ability to easily manipulate them genetically, has made the fruit fly a useful model organism to study cancer biology. In this review we outline the basic mechanisms and signaling pathways conserved between humans and flies responsible of inducing uncontrolled growth and cancer development. Second, we describe classic and novel Drosophila models used to study different cancers, with the objective to discuss their strengths and limitations on their use to identify signals driving growth cell autonomously and within organs, drug discovery and for therapeutic approaches.

What is the oncogene that is activated in adenomas?

Another aggressive oncogene that is hyper-activated upon Apc loss, in mouse and human intestinal adenomas is the non-receptor tyrosine kinase c-Src (Yeatman, 2004 ). This proto-oncogene is amplified or activated in more than 20% of human tumors, and its activity has been demonstrated to play a central role in the formation of colorectal cancer (CRC). In mice, expression of c-Src increases in the proliferative progenitor cells of the “cripta” favoring hyperplastic adenoma formation (Cordero et al., 2014 ). In Drosophila the expression of c-Src orthologs ( Src42A and Src62B) induces proliferation of the ISCs cells in wild-type animals, and reduction of their expression is sufficient to inhibit ISCs' hyper-proliferation of Apc mutant cells (Cordero et al., 2014 ). Notably, these results recapitulate an important part of the function of mammalian c-Src in the progenitor cells of the intestine during homeostasis and adenoma formation, suggesting a conserved role of this gene in flies in controlling proper ISCs proliferation.

What is the target of rapamycin?

The PI3K/Target of rapamycin (TOR) signaling pathway is a highly conserved key regulator of growth. The binding of insulin-like peptides (ILPs) (fly's insulin) to the receptor (InR) results in the phosphorylation of chico /IRS1-4, and the production of phosphatidylinositol-3, 4,5-triphosphate (PIP3) by PI3K, a reaction that is counteracted by the lipid phosphatase PTEN (Grewal, 2009 ). PIP3 recruits several Ser/Thr kinases to the plasma membrane, including Akt/PKB and PDK1 (3′-phosphoinosite-dependent protein kinase-1), while its activation results in the inhibition of Glycogen Synthase Kinase-beta (GSK3-β), a conserved kinase that not only controls energy metabolism by inactivation of Glycogen Synthase, but also regulates Wnt signaling by controlling β-catenin/ armadillo (Xu et al., 2009) and Myc stability (Bellosta and Gallant, 2010 ). Activation of Akt also inhibits Tuberous Sclerosis Complex 1 and 2 (TSC1/2), a tumor suppressor binary complex that negatively regulates Rheb, a GTPase upstream of TOR kinase responsible for the activation of TORC1. TOR is found in two complexes: TORC1, which includes Raptor and LST8 adaptor molecules, is sensitive to amino acids and is inhibited by rapamycin; and TORC2, that is composed of LST8 and Rictor adaptor molecules, and does not respond to amino acids or rapamycin (Saxton and Sabatini, 2017 ). Activation of TORC1 results in phosphorylation of ribosomal protein kinase p-70-S6 (S6K) and of eukaryotic translation initiation factor 4E-binding protein-1 (4E-BP1), thereby triggering protein synthesis and initiation of translation. Insulin and TOR activities are also balanced by a negative feedback mechanism that is activated when S6K is hyper-activated to counteract insulin activity. Under this condition, S6K phosphorylates IRS1-4/ chico triggering its internalization and subsequent proteasomal degradation. This feedback mechanism is reduced in pathological conditions, such as the Tuberous Sclerosis Complex syndrome (TSC), where cells carrying tsc1 or tsc2 mutations display an abnormal increase in size and exhibit constitutive phosphorylation of S6K (Saxton and Sabatini, 2017 ). As members of PI3Ks and TOR signaling are frequently activated in human tumors, they are attractive targets for cancer treatment.

How do cancer cells survive?

Cancer cells also exhibit alterations in metabolic pathways that contribute to their survival. Rapidly proliferating cells have a high metabolic rate and suffer from low oxygen conditions (hypoxia). In epithelial tumors, this condition triggers the so-called angiogenic “switch” where the quiescent vascular network is induced to proliferate by the secretion of pro-angiogenic factors, such as VEGF (Vascular Endothelial Growth Factor) and FGF (Fibroblast Growth Factor) (Hida et al., 2018 ), allowing the formation of new vessels that penetrate into the tumor mass to supply oxygen and nutrients (Carmeliet and Jain, 2011 ). Cancers cells also exhibit a metabolic switch where they reprogram their metabolism to use an alternative and less abundant anabolic pathway to sustain their growth. In particular they switch from oxidative phosphorylation to anaerobic glycolysis, where glucose is used to produce lactate, through a process called the “Warburg effect” (Pavlova and Thompson, 2016; Vander Heiden and DeBerardinis, 2017 ). This metabolic switch is not yet completely characterized but is supported by the activation of oncogenes, including Myc that also activates glutaminolysis to fuel the TCA cycle with anaplerotic reactions to produce the intermediates necessary for cellular biosynthesis (Hsieh and Dang, 2016 ).

What Is a Drosophila Melanogaster?

Frequently referred to as a fruit fly, it is usually found flying around your fruit bowel, especially if the fruit has been there for a long time. They are usually about 0.3cm long and although they are a huge frustration for us, as previously mentioned they are a huge part of biological research in most laboratories that focus on genetic research. In fact, recent studies show that there are over 7000 scientists that study this bug worldwide as a fulltime job. In fact, research made on the fruit fly and how it has helped improve our understanding of genetics earned a Nobel prize in medicine in the 1990’s.

Why do scientists use fruit flies as a model for genetic research?

Here are a few reasons why scientists use the fruit flies DNA as a model for genetic research. Fruit flies breed quickly and cost almost nothing to grow thousands at a time in a controlled environment. In addition, the female fruit flies lay up to 400 eggs every 16 days or so which helps the population grow quickly .

Why are fruit flies important?

Fruit flies have played a major part in the advancement of genetic research. In fact, without the help of these fruit flies, the speed in which we have come to understand other parts of genetics (including humans) would have been severely reduced. So although they might be very frustrating for you, just remember that they serve a very important role in science. I hope that this has been informative and I would like to thank you for taking the time to read my article on the amazing facts about the Drosophila Melanogaster.

What is a fruit fly?

Drosophila Melanogaster are now referred to as the common term “fruit flies” or “vinegar fly”. Although they may seem to just be a nuisance, they are the most widely studied and researched bug in the world. Major fields of study include microbial pathogenesis and genetics. One of the primary reasons why fruit flies are so widely studied is due ...

What is the color of a fruit flies eyes?

Drosophila Melanogaster Anatomy. Drosophila Genetics. Regular fruit flies have red eyes and their bodies are generally a mixture between brown and yellow. Their general length is about 0.3cm. Usually the male fruit flies have a slightly darker body then the females.

What is the color of the eyes in Drosophila?

Drosophila Melanogaster Eye Color. The two main types of eye color are created using two different pathways, the Drosopterin pathways is responsible for creating the red color, whereas the ommochrome pathway is responsible for the creation of the brownish colors.

Why are fruit flies studied?

One of the primary reasons why fruit flies are so widely studied is due to their extremely fast breeding rate. Since a entire new generation of fruit flies can come into existence in less then 170 hours, it is no wonder that they are examined closely.

What color is DAPI?

Stained are: DAPI (blue ) to show the DNA, WGA-657 (green) to show membranes, primarily visible are nuclear membranes. Also stained by fluorescent in situ hybridization is the oskar mRNA that is enriched at the posterior cortex. Detection: Cy3-coupled tyramide amplification.

How long does it take for a fruit fly to grow?

The fruit fly is simple to work with, with a relatively short lifecycle/generation time of 12 days and its small size allows it to be produced in large numbers. These practical considerations make it suitable for many studies. The fruit fly is well understood at the phenotype level and has a simple genome, enabling molecular genetics studies. Despite this, it still has ~60% of the genes involved in human genetic diseases and some cancers.

What percentage of the genes are in fruit fly?

Despite this, it still has ~60% of the genes involved in human genetic diseases and some cancers. The fruit fly has also been used as a model for more complex studies, such as development and processes involved in cognitive behaviour, memory and learning studies. Recently it has been used in studies on wound repair and infection prevention. [2] .

What is the fruit fly?

In the laboratory, the fruit fly has been a key model organism since the very first studies of genetics. It was the humble fruit fly that provided us with information on genetic inheritance of chromosomes at the phenotype level.

What does a drosophila eat?

The Drosophila feeds and breeds on fermenting fruit or on other sources of fermenting sugar such as waste in drains or rubbish bins. The story of Drosophila in biological research began in the early years of the 20th century.

What is the relationship between fruit fly and human genes?

The relationship between fruit fly and human genes? is so close that often the sequences of newly discovered human genes, including disease genes, can be matched with equivalent genes in the fly. 75 per cent of the genes that cause disease in humans are also found in the fruit fly.

How long does it take for a fruit fly to reproduce?

Drosophila have a short, simple reproduction cycle. It is normally about 8-14 days, depending on the environmental temperature. This means that several generations can be observed in a matter of months.

What is the most well known model organism?

The fruit fly ( Drosophila melanogaster) is one of the most well understood of all the model organisms.

What is the chromosome of Drosophila?

Drosophila have ‘polytene’ chromosomes, which means that they are oversized and have barcode-like banding patterns of light and dark. During early Drosophila research scientists could therefore easily identify chromosomal? rearrangements and deletions under the microscope.

How small are fruit fly?

Fruit fly are small (3 mm long) but not so small that they can’t be seen without a microscope. This allows scientists to keep millions of them in the laboratory at a time. They are inexpensive to maintain in the laboratory.

What color are Drosophila's eyes?

Adults in the wild are tan with black stripes on the back of the abdomen and vivid red eyes. However, there are many visible genetic mutations? , including many different eye colours, which are valuable for geneticists studying Drosophila.

Why did Morgan use fruit flies?

Morgan decided to use fruit flies to study how physical traits (for example, eye color) were transmitted from parents to offspring, and he was able to elegantly show that genes are stored in chromosomes and form the basis of heredity . This work won him a Nobel prize in 1933 and marked the birth of modern genetics.

What did Sarah Palin say about the fruit fly?

January 19, 2019. During the 2008 US election campaign, governor Sarah Palin famously said that public funding was being wasted on projects like “fruit fly research”. This comment sparked anger in the scientific community, and the vice-presidential candidate was mocked for her ignorance.

What did Morgan do in 1933?

This work won him a Nobel prize in 1933 and marked the birth of modern genetics. But what really impressed Morgan’s colleagues was how fast he obtained his results- while other geneticists could spends years on a single experiment using traditional model organisms like chicken, mouse or plants, Morgan did several experiments with flies in just ...

Why is the book "First in Fly" called "First in Fly"?

The book featured in this post, by Stephanie Elizabeth Mohr, is entitled “First in fly” because so many important genes in humans were first discovered in Drosophila. And even though the scientists making these discoveries didn’t know it at the time, several of these genes are implicated in biological processes in humans and in diseases such as cancer, diabetes, Down’s syndrome, and neurodegenerative diseases like Alzheimer’s, Parkinson’s and others.

Do fruit flies have Alzheimer's?

Although fruit flies don’t normally develop Alzheimer’s, their brains have the same genes and molecular machinery involved in the human disease. So scientists can study how the progression of Alzheimer’s (and other age-related diseases) in the fruit fly within just a few weeks.

Do fruit flies have mutations?

Fruit flies (Drosophila melanogaster) with mutations that modify the colour of the eyes or body (Credit: Wikipedia Commons). And because female flies can lay dozens of eggs every day, essentially producing thousands of offspring over the course of a lifetime, Morgan could quickly verify his data on very large samples.

Do fruit flies have the same genes as humans?

But there is another important reason: although fruit flies and humans look very different, they share many of the same gene network s and biological processes. For example, flies have about 75% of the genes known to cause disease in humans, which means we can study disease and test medical drugs in flies, quickly and cheaply.