#plos genetics

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An Important Development

The journey towards making the next generation starts at the very earliest stages of life. Certain special cells, known as germ cells, that will go on to form eggs or sperm in the adult are marked out in every embryo within the first few days of development. Researchers have discovered that zebrafish embryos with a faulty version of a gene called Igf2bp3, like the one shown here, usually develop as males. If any do become females, then they tend to have defective eggs. Looking more closely, they noticed that a region called the yolk syncytial layer, sandwiched in between the green and blue parts in this image, is larger than normal in these defective embryos, which could explain why they don’t develop properly. The Igf2bp3 gene has counterparts in other species, including our own, so this research could shed light on problems with sex development and infertility in humans too.

Written by Kat Arney

Image from work by Yin Ho Vong and colleagues, on the cover of PLOS Genetics, August 2021

Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in PLOS Genetics, July 2021

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Going Dark

Three million years without sunlight has made a big impact on these Somalian cavefish, which live in complete darkness in underwater caves. Not only have they lost their eyes and skin pigmentation, but evolving in the dark has had an impact on the inner workings of their cells too. Cavefish obviously don’t suffer damage to their DNA from the ultraviolet rays in sunlight in their deep, dark homes, so they’ve lost the main light-dependent molecular repair ‘toolkit’ that other surface-dwelling animals rely on to fix these faults, known as photoreactivation DNA repair. However, they still retain a different mechanism known as nucleotide excision repair, which can be switched on if the cavefish are exposed to light. Comparing these processes in cavefish with the DNA repair systems in daylight-living zebrafish helps to illuminate the changes that have happened during their evolutionary journey over millions of years in such a strange environment.

Written by Kat Arney

Image by Hectonichus via Wikimedia

Research by Haiyu Zhao et al, Institute of Biological and Chemical Systems, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany

Image originally published with a Creative Commons Attribution Attribution-ShareAlike 3.0 Unported (CC BY-SA 3.0)

Research published in PLOS Genetics, February 2021

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Stress Protection

Deep inside a fruit fly larva are the cellular ‘seeds’ of the adult insect: structures known as imaginal discs, which sit quietly until it’s time to transform into a fly. In the meantime, it’s vital that these important cells are maintained and protected to avoid causing problems in building an adult body. On the left is the wing imaginal disc from a normal fly, while the one in the middle is lacking a gene called headcase and the one on the right also has an extra dose of another gene that has been implicated in cancer. Researchers have discovered that headcase helps to protect imaginal disc cells from stress, and also triggers them to develop into adult structures. Versions of headcase are found in many other animals, including humans, so it could be playing a role in protecting our cells from stressful conditions that can induce the growth of cancer.

Written by Kat Arney

Image by Panagiotis Giannios and Jordi Casanova

Institut de Biologia Molecular de Barcelona (CSIC), Barcelona, Catalonia, Spain

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in PLOS Genetics, February 2021

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Eye Say

Our eyes work by focusing light through the lens at the front of the eyeball onto a layer of light-sensitive cells (retina) at the back. Having eyeballs that are too small relative to where the lens focuses light results in far-sightedness. Some people are born with a fault in a gene called TMEM98, which causes a condition known as nanophthalmos – Greek for ‘very small eye’. This leaves them severely far-sighted and can eventually lead to loss of vision altogether. To find out more about how faults in TMEM98 affect eyeball size, researchers have been studying mice carrying a similar fault in the gene to that found in human patients. Curiously, the eyeballs in these animals are unusually large and misshapen (right) compared with healthy mice (left), rather than being abnormally small. The findings suggest that other genes are also involved in nanophthalmos, highlighting the genetic complexity of the eyeball-building process.

Written by Kat Arney

Image from work by Sally H. Cross and colleagues

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK

Image originally published under a Creative Commons Licence (BY 4.0)

Published in PLOS Genetics, April 2020

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Wave Machine

These delicate waving pink fronds are cilia – tiny hairs on the surface of the cells lining the airways. They effectively act as tiny ‘brushes’, sweeping away gunky fluids containing nasty stuff like trapped bacteria, viruses and dirt. Cilia are found in other parts of the body that need help keeping things moving, such as the fallopian tubes that carry eggs to the womb, or the fluid-filled cavities in the brain. People with the rare genetic condition primary ciliary dyskinesia (PCD) have defective cilia, causing a range of health problems including lung disease and infertility. While around 40 specific gene faults responsible for PCD have been found, accounting for around 70% of patients, many are still left without an explanation. Researchers have now found that faults in a gene called CFAP57 cause PCD – the first time that this gene has been linked to the condition – pointing towards new ideas for treatment.

Written by Kat Arney

Image from work by Ximena M. Bustamante-Marin and Amjad Horani, and colleagues

Department of Pathology and Laboratory Medicine and the Marsico Lung Institute, University of North Carolina, Chapel Hill, NC and Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in PLOS Genetics, August 2020

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Two Can Play

These alien-like creatures are zebrafish larvae, just five days old. Their blue ‘lips’ are actually the developing pituitary gland, stained to reveal the activity levels of a gene called pro-opiomelanocortin (pomca for short). They’re helping scientists figure out the interaction between the response to low oxygen levels within tissues (hypoxia), which is linked to diseases such as asthma and rheumatoid arthritis, and anti-inflammatory drugs called glucocorticoids that are commonly used to treat them. The animal in the top left picture is genetically normal, while the top right one lacks a gene involved in the hypoxia response. The larva on the bottom left is missing a gene that responds to glucocorticoid drugs and the last one is lacking both. By measuring the impact of these genetic changes on pomca activity, researchers can start to tease out the interplay between hypoxia and glucocorticoids to develop more effective anti-inflammatory drugs in the future.

Written by Kat Arney

Image adapted from work by Davide Marchi and colleagues

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

The Bateson Centre & Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, UK

Published in PLOS Genetics, May 2020

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Teamwork Works

When it comes to building a living organism, teamwork is key. Many different molecules have to work together to make sure that the right parts grow in the right place at the right time. In the case of developing fruit flies (Drosophila), some of these components are pre-packaged in the egg ready to spring into action once it's fertilised. Some of them play a particularly important role in setting up the basic pattern of the embryo, with the head at one end and the tail at the other. These images show Drosophila egg chambers stained with fluorescent dyes that highlight various molecules involved in early embryo development. By figuring out where each molecule appears (green or red) and where they overlap (yellow), researchers can start to understand how they get located in the right place in the egg and tease out how they interact together to make an embryo.

Written by Kat Arney

Image adapted from work by Annabelle Dold, Hong Han and Niankun Liu, and colleagues

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

RNA Epigenetics, Institute of Molecular Biology, Mainz, Germany and Department of Biology, McGill University, Montréal, Québec, Canada

Published in PLOS Genetics, January 2020

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Clearing Things Up

You can appreciate the essential role a brain surgeon is performing without understanding exactly how they do it. The same applies to molecules in the body, such as the enzyme PRPS, which researchers know is integral to several neurological diseases, but don’t fully understand. Unpicking its role could spark new treatments, so researchers blocked its action in fruit flies to see what processes were affected. Flies lacking the enzyme starved more quickly in tests, because they couldn’t digest fat stored in lipid droplets (red, unchanged after 48 hours of starvation in test flies, bottom right, compared to before starvation, left, and unaltered flies, top). This reveals PRPS is needed for autophagy – a process involved in disassembling cells, maintaining a stable internal environment, and known to be involved in nervous system disorders such as Parkinson’s. Revealing this and other mechanisms of PRPS is the first step in tackling its unwanted effects.

Written by Anthony Lewis

Image adapted from work by Keemo Delos Santos and colleagues

Department of Biology, Developmental Biology Research Initiative, McGill University, Montreal, Quebec, Canada

Image originally published under a Creative Commons Licence (BY 4.0)

Published in PLOS Genetics, September 2019

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