# Model system: the fruit fly

> Above all the fruit fly, Drosophila melanogaster: its egg chambers in the ovary and its earliest embryo, at the moment the embryo’s own genes take over from…

Source: https://khushisingh.in/research/model-system/
Author: Khushi Singh (khushisingh.in). Licence: CC BY 4.0 for text and original illustrations, unless a credit says otherwise.
Evidence labels used on this site: established, strong evidence, emerging, hypothesis, debated. Where a page has Simple, Curious and Expert versions, all three follow.

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Research · Model system

Above all the fruit fly, Drosophila melanogaster: its egg chambers in the ovary and its earliest embryo, at the moment the embryo’s own genes take over from its mother’s. Here is why biologists use it, how it develops, the tools that make it powerful, and the other organisms and proteins I have worked with.

Main model organism

## *Drosophila melanogaster*, the fruit fly

Most of my research has followed the fly from egg chamber to early embryo: oogenesis in the ovary, and embryogenesis up to stage 5, when the maternal-to-zygotic transition hands control from the mother’s RNAs and proteins to the embryo’s own genes.

Projects: [Microbes, lactate and inheritance](https://khushisingh.in/research/gut-to-germline/) · [Behaviour: activity and sleep](https://khushisingh.in/research/behaviour-and-metabolism/) · [oskar RNA condensates](https://khushisingh.in/research/oskar-condensates/) · [ER shape and autophagy](https://khushisingh.in/research/er-and-autophagy/) · [NCBI Taxonomy 7227](https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=7227)

1. 1 Egg chamber, stage 9: oskar marks the germ plasm
2. 2 The mature egg
3. 3 Embryo, stage 5: cells form as the embryo’s genes switch on

- ≈ 10 daysfrom egg to adult at 25 °C
- ≈ 14,000protein-coding genes on four chromosome pairs
- 14stages of egg-chamber development in the ovary
- 1 + 15oocyte and nurse cells in every germline cyst
- 13nuclear divisions before the embryo forms cells
- ≈ 6,000cells form at once in the stage 5 embryo
- 130–170minutes after egg laying: stage 5, at 25 °C

From FlyBase (Öztürk-Çolak et al. 2024; stage definitions FBdv), Adams et al. 2000, Jennings 2011, Bastock & St Johnston 2008, Foe & Alberts 1983 and Mazumdar & Mazumdar 2002.

### Why biologists use it

Flies breed fast, about ten days from egg to adult at 25 °C, and are cheap to keep in large numbers. Their genome was sequenced in 2000, with about 14,000 protein-coding genes on four pairs of chromosomes, and most human disease-associated genes have a recognisable counterpart in the fly. Genetic switches turn a chosen gene on or off in a single tissue. The germline is set aside very early by the germ plasm at the back of the egg, so what a mother puts into her egg can be followed into the embryo.

- Of 929 human disease genes checked, 77% had a recognisable match in the fly genome (Reiter et al. 2001); a later estimate is about 65% (Ugur et al. 2016). (evidence: established)
- The GAL4/UAS system switches a chosen gene on in a chosen tissue (Brand & Perrimon 1993). (evidence: established)

### Life cycle

At 25 °C an egg hatches after about a day; the larva feeds and grows through three stages for about four days, then forms a pupa, in which the adult body is built over about four more days. Adults live for one to two months, and a female can lay up to about 100 eggs a day (Jennings 2011). (evidence: established)

### From egg chamber to embryo

**Oogenesis.** In the ovary, a germline stem cell divides to make a cyst of 16 connected cells: one becomes the oocyte and 15 become nurse cells, which pour their RNAs and proteins into it. Somatic follicle cells wrap the cyst into an egg chamber, which passes through 14 stages. Along the way, mRNAs such as *oskar* and *bicoid* are placed at the back and front of the oocyte, laying down the future body axes and the germ plasm (Bastock & St Johnston 2008). (evidence: established)

**Embryogenesis to stage 5.** After fertilisation the nuclei divide 13 times in about two hours without forming cells, sharing one cytoplasm (Foe & Alberts 1983). Pole cells, the future eggs and sperm, bud off at the back. In stage 5, membranes grow between about 6,000 nuclei at once, and the embryo strongly switches on its own genes, helped by the pioneer factor Zelda (Liang et al. 2008), while maternal mRNAs are cleared: the maternal-to-zygotic transition (Vastenhouw et al. 2019). (evidence: established)

Step through oogenesis, the hand-over from egg to embryo, and the first seven embryonic stages. Stage 5, the cellular blastoderm at the maternal-to-zygotic transition, is where most of my work sits.

*[Here the web page has an interactive activity; open the source URL to use it.]*

### Stage 5 in 3D

About 6,000 nuclei sit just under the surface of the stage 5 embryo. Pick a gene to see where it is switched on, from the maternal *bicoid* gradient to the seven stripes of *even-skipped*, made by the embryo’s own genome.

*[Here the web page has an interactive 3D model; open the source URL to use it.]*

### The genetic toolkit

- **Switch a gene on in one tissue.** GAL4/UAS: a “driver” line decides where, a “responder” line decides which gene. Cross them and the gene is active only where the driver works (Brand & Perrimon 1993).
- **Turn a gene down.** Genome-wide collections of RNAi lines let researchers reduce almost any gene, in a chosen tissue, with GAL4 (Dietzl et al. 2007; Perkins et al. 2015).
- **Edit the genome.** CRISPR/Cas9 tools for flies make precise mutations, tags and deletions in the germline or in single tissues (Port et al. 2014).
- **Keep complex stocks for years.** Balancer chromosomes carry inversions that block recombination and visible markers such as curly wings, so combinations of mutations can be kept and recognised by eye (Kaufman 2017).
- **Shared resources.** FlyBase collects genes, expression data and stocks (Öztürk-Çolak et al. 2024); public stock centres send fly lines worldwide.

Try the logic of GAL4/UAS: pick a driver (where) and a responder (what).

*[Here the web page has an interactive activity; open the source URL to use it.]*

### Discoveries made in flies

1. 1933 Genes sit on chromosomes (Thomas Hunt Morgan)
2. 1946 X-rays cause mutations (Hermann J. Muller)
3. 1995 Genes that build the embryo’s body plan (Edward B. Lewis, Christiane Nüsslein-Volhard, Eric F. Wieschaus)
4. 2011 How innate immunity is switched on, first found through Toll in flies (Jules A. Hoffmann, shared prize)
5. 2017 The molecular clock behind circadian rhythms (Jeffrey C. Hall, Michael Rosbash, Michael W. Young)
6. 2024 A wiring diagram of a whole adult fly brain: 139,255 neurons (Dorkenwald et al. 2024)

Nobel Prizes in Physiology or Medicine, from nobelprize.org; 2024 from Dorkenwald et al. 2024.

### The adult fly in 3D

*[Here the web page has an interactive 3D model; open the source URL to use it.]*

A stylised model built in code. Real flies are about 2.5 mm long.

### What I did

**Worked with:** Oogenesis (egg chambers in the ovary) and early embryogenesis, above all stage 5 embryos at the maternal-to-zygotic transition.

- Reduced an ER-shaping protein by RNAi and studied autophagy, ubiquitination and tissue structure in embryos and ovaries (IISER Pune, 2024–2025).
- Optimised single-molecule FISH to image oskar RNA condensates in embryos (IIT Kharagpur, 2025).
- Now asking whether metabolism shapes histone marks in the early embryo, and how it shapes activity and sleep (MPI-IE, 2026–2027, ongoing).

## Other organisms and proteins

### Insects and plants on the iiser pune campus

Field work

A field project on how insects respond to light and how plants and their pathogens interact across the campus (IISER Pune, 2023). It is where the habit of careful observation began.

[Ecology and evolution](https://khushisingh.in/research/ecology-first-steps/)

### Proteins from other species

In these projects I worked with purified proteins in the test tube, not with the organisms themselves. Borrowing a protein from the species where it is easiest to study is common in biochemistry.

- #### *Escherichia coli*
  Gut bacterium and lab workhorse
  PstS, the phosphate-binding protein
  Engineered and labelled with a dye so that it glows brighter when it binds phosphate: a real-time phosphate sensor (Brune et al. 1994).
  **What I did:** Prepared, labelled and calibrated the sensor (IISER Pune, 2025–2026).
  [Phosphate biosensor and FtsZ](https://khushisingh.in/research/phosphate-biosensor-ftsz/) · [NCBI Taxonomy 562](https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=562)
- #### *Spiroplasma melliferum*
  A bacterium without a cell wall
  FtsZ
  The bacterial cousin of tubulin, which forms the ring that divides a bacterium in two (Bi & Lutkenhaus 1991).
  **What I did:** Followed its use of GTP in real time with the phosphate sensor and fitted the kinetics (IISER Pune, 2025–2026).
  [Phosphate biosensor and FtsZ](https://khushisingh.in/research/phosphate-biosensor-ftsz/) · [NCBI Taxonomy 2134](https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=2134)
- #### *Mus musculus*
  House mouse
  Prion protein (PrP)
  A normal protein of nerve cells that can misfold and spread in prion diseases (Prusiner 1998).
  **What I did:** Mapped the salt, pH and protein concentrations at which purified PrP forms liquid droplets or clumps (IISER Pune, 2024).
  [Prion protein phase separation](https://khushisingh.in/research/prion-phase-separation/) · [NCBI Taxonomy 10090](https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=10090)

[← All research](https://khushisingh.in/research/) · [The methods (toolbox)](https://khushisingh.in/research/toolbox/) · [Policy brief: why model organisms are worth investing in](https://khushisingh.in/policy/briefs/small-organisms-big-returns/)

## References

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