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Novel zebrafish disease model used to find the cause of a rare form of childhood Parkinsonism

Lead author of the study, Dr Karin Tuschl of the Wilson lab explains: “A new genome editing method called CRISPR/Cas9 was used to study the role of the transporter in zebrafish and showed that when the SLC39A14 gene is disrupted, there is a build-up of manganese in the brain and impaired motor behaviour similar to that seen in humans. This important observation confirmed that we had indeed identified the disease-causing gene in our patients. Our findings provide families with a genetic diagnosis for their children’s condition, thereby facilitating counselling for future pregnancies.”

 

Read more on the UCL website here

Read the publication in Nature Communications here

Research image featured on the BBC website

A research image from the Zebrafish Brain Atlas (zebrafishbrain.org) by PhD student Kate Turner is featured in a BBC article on tracking cells in the embryo

Brain asymmetry improves processing of sensory information

Our brains are asymmetric but does this matter for effective cognitive function?

Elena Dreosti, Steve Wilson and colleagues think it does.

By imaging activity of individual neurons in larval zebrafish they found a region of the brain in which most neurons responding to a light stimulus were on the left whereas most responding to odour were on the right (Figure 1).  In brains that were symmetric with either double-left or double-right character, they observed that responses to odour or to light were almost absent.  These results show that loss of brain asymmetry can have significant consequences upon sensory processing and circuit function and raises the possibility that defects in the establishment of brain lateralization could be causative of cognitive or other symptoms of brain dysfunction.

Figure 1. Examples of neuronal activity in the left and right habenular nuclei (L Hb and R Hb) of four different four-day old fish with normal left-right habenular laterality (LR), reversed laterality (RL), symmetric double-right (RR) and symmetric double-left (LL) habenulae showing lateralization of neuronal responses to light and odour.  Neuronal cell bodies are shown as dots colour-coded in red, blue, violet, or white depending on whether they responded to light, odour, both light and odour, or were non-responding.

Original article: Dreosti E., Llopis, N., Carl M., Yaksi E. & Wilson S.W. (2013) Left-right asymmetry is required for the habenulae to respond to both visual and olfactory stimuli. Current Biology http://dx.doi.org/10.1016/j.cub.2014.01.016

Further reading In The Press: Science 20, Counsel & Heal, UCL
Publication summary here

Seeing is believing – watching eyes take shape

Despite looking nothing like brain tissue, our eyes initially form as outgrowths from the brain
during embryonic development. New research from Kenzo Ivanovitch, Florencia Cavodeassi and
Stephen Wilson has revealed how prospective eye cells initiate their journey from the brain to the
eye sockets. They reasoned that two criteria must be met for successful outgrowth of the eyes:
first, eye forming cells must initiate a behavioural programme distinct from adjacent territories in
the brain; and second, that future eye cells must not intermix with other brain cells. To investigate
these issues, the UCL researchers used very high-resolution microscopy to resolve the behaviours
of individual eye forming cells in transparent zebrafish embryos that are eminently well-suited for
such imaging analyses. They discovered that the eye-forming cells precociously organise as a
polarised sheet of cells (an epithelium) when compared to cells in neighbouring brain regions, and
that this behaviour is essential for the proper evagination of the primordia of the eyes. They further
unravelled a molecular mechanism that ensures that the eye-forming cells are prevented from
intermixing with adjacent brain cells as the eyes begin to take shape. This work is paving the way
for a better understanding of eye morphogenesis and organogenesis and is published in papers in
the journals Development and Developmental Cell.

Figure 1. Image of a head-on view of the brain of a zebrafish embryo just as the prospective eye cells (green) start to push out laterally to form the optic vesicles.   The orange labelling is Laminin, a protein present at the outer surface of the eye cells that is necessary for proper outgrowth.

Figure 2. Sequential images from a movie in which prospective eye cells (green) reorganise and move outwards from the brain to form the nascent eyes (optic vesicles).

 

Movie 1. Time-lapse movie of prospective eye cells bulging out from the brain (including telencephalon and hypothalamus) to form the nascent eyes (optic vesicles).  The membranes of the cells are labelled green and the cell nuclei in red.

Original papers:

Cavodeassi, Ivanovitch and Wilson (2013). Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis. Development, 140:4193-202.
Ivanovitch, Cavodeassi and Wilson (2013). Precocious acquisition of neuroepithelial character in the eye field underlies the onset of eye morphogenesis. Developmental Cell, 27:293-305.

Summer Challenge in the Wilson lab

Ana, Ricardo and Kate have organised a course on “Cell Biology in the Zebrafish Lab’ for the Year 12 UCL Summer Challenge. The aim of the UCL Summer Challenge is to increase access to UCL for students from under-represented backgrounds by helping them to develop their independent research, critical thinking, academic writing and presentation skills. The course was fully booked up, and the students have been getting hands on experience in zebrafish research, learning about brain development, sleep and behaviour and looking at some of our mutant and transgenic lines.

Dr Rihel on the Radio

Dr Jason Rihel discusses the biological significance of zebrafish on BBC Radio4′s Material World Program (April 18th) along with Dr. Stemple from the Sanger Institute.

Why is the zebrafish so important for genetic research?

“It’s a compromise between having the complexity to model some of the things that we want to study – brain function, behaviour, … – but also the simplicity that we might be able to understand it.” said Dr Jason Rihel (UCL Cell & Developmental Biology).  Listen here from 11 mins (to download right click and “save target as/link as”).

Masa Tada awarded a 5-year programme grant

Dr Masa Tada has been awarded a 5-year Cancer Research UK-funded programme grant, jointly with Paul Martin at the University of Bristol, to study the earliest interactions of host with pre-neoplastic cells in Zebrafish. This programme of projects investigates how epithelia can extrude pre-neoplastic cells (Tada Lab) and how the host innate immune system interacts in positive and negative ways with these cells (Martin Lab). A post-doc position is available in Tada Lab. Please contact Masa for details.

science and beauty in the zebrafish

The Wilson lab’s Kate and Tom discuss why the zebrafish is a beautiful organism to work on in this short film by the Wellcome Trust.

New paper helps unravel the mysteries behind brain diversity

Morphogenesis underlying the development of the everted teleost telencephalon.
Monica Folgeira, Steve Wilson and John Clarke
September 2012

Brain diversity has puzzled scientists for centuries. But, what do we mean by “brain diversity”? If one compares brains from many different species of vertebrates, soon one realizes how different they look. This diversity in brain form or morphology is extraordinary not only for brains from very separate groups (e. g. mammals vs. fishes), but also within the same group.

Take as an example “ray-finned fishes”, a group of fishes with more than 30,000 species and whose members have fins supported by bony spines. Within this group, brain morphology can be very different even between closely related species. In order to understand how brain diversity is generated, we studied in detail the development of the telencephalon of the zebrafish (a ray-finned fish).

For full details see publication summary.

 

Leonardo Valdivia wins award for best PhD thesis in Cell Biology

“In Chile, in order to encourage the scientific training in the country and promote the academic excellence, the Chilean Foundation for Cell Biology together with the Chilean Society of Cell Biology annually reward the best PhD. thesis in the global area of Cell Biology (Molecular Biology, Neurobiology, Immunology, Biotechnology, Developmental Biology etc..). My thesis was awarded this year (2012)

I was presented with the award in the XXVI Annual Meeting of the Chilean Society for Cell Biology in Puerto Varas, Chile (October, 2012). I gave a talk entitled “Identification of essential genes for lateral line development and mechanosensory hair cell differentiation in zebrafish”, for which I received a flight ticket to Chile and 2000 US dollars. The idea of this award is getting in touch with Chilean groups of my interest, to show what I’m currently doing and keeping in touch with Chile to be back there after my postdoc.”

For more details see our publication summaries page.

 

Jason Rihel brings zebrafish sleep research to UCL

UCL are excited to announce the arrival of a new research group – the Rihel Lab.
They study the genes and neuronal circuits that regulate sleep in zebrafish.

See their page for full details

Steve Wilson Group win 2 awards at the Wellcome Image Awards 2011!

Two zebrafish images from the Wilson Lab were recently honored at the 2011 Wellcome Image Awards.

The Wellcome image collection is an extensive resource, containing thousands of science-related images. Every year, a small subset of recently acquired images are chosen by a panel of judges as the most scientifically informative, technically excellent, and aesthetically striking images. This group of twenty award-winning images – containing two striking micrographs from the Wilson lab – is on display at the Wellcome Collection until the 10th of July 2011. They can also be viewed and downloaded from the Wellcome Image Collection Website.

Monica Folgueira recently captured this confocal micrograph of a 5 day old cavefish embryo that highlights some of the inner-workings of the fish nervous system. The embryo has been stained with an antibody against a calcium-binding protein (calretinin, in green) to show different neuronal types and their processes in the nervous system, and with an antibody against a component of tight junctions (zona occludens- 1, in red). Although the eyes are very evident at this stage, they will not develop any further. The image also shows an special character of fish: the presence of taste buds outside the oral cavity, around the lips and along the body.

This photomicrograph, captured by Kara Cerveny, shows a lateral image of a 3 day old zebrafish retina from the eye of a three-day-old zebrafish (Danio rerio). Using double in situ hybridisation, the undifferentiated retinal stem cells have been highlighted in red while the retinal progenitor cells that are beginning to differentiate are highlighted in purple. The kaleidoscope-like effect is created by the elongated neuroepithelial cells radiating from the undifferentiated region closest to the lens towards the differentiated cells deeper in the retina. This image depicts the whole eye and was created by reflecting half the image across its origin.

See Wellcome website for more info

 

Zebrafish in music

We’ve all heard that scientists are working in laboratories around the world, experimenting and solving problems, but what exactly are scientists doing on a daily basis? Our lab was one of six UCL biomedical science labs that helped Wellcome Trust sponsored artist, Gethan Dick, discover what it’s like to be a research scientist. This cooperative project produced an album of six songs – all truthful, poetic representations of different types of research ranging from basic developmental neurobiology to clinical studies using functional MRI.

Hear about our research on eye development by listening to Fish Eye/Fix Me, the track composed by Gethan Dick and Hannah Marshall in collaboration with Wilson lab post-doctoral fellow, Kara Cerveny. You can check out all of the songs on the album Trying and Trying and Trying.

Kara says, “Gethan captured the essence of my lab work, right down to the way I hold my breath when moving cells from one embryo into another. In the past, I have often found that words are no substitute for actually showing someone what it means to pipette, to transplant cells, to look through a microscope, to cut frozen sections. With this track, Gethan has used words to paint pictures of these exact things. Fish Eye/Fix Me is an evocative, haunting, and truthful piece about the life of a developmental biologist, investigating the environmental signals that override mutations and rescue sick cells from their intrinsic cell death program.”

Link to the song and the album.

New Paper on Retinal Stem Cells, Proliferation and Cancer

Nearly 40 years after US President Richard Nixon declared ‘war on cancer’, researchers around the world are still trying to understand how tumors form and grow. New insight into how cells can be prevented from becoming cancerous is found in an unlikely place – the eyes of zebrafish.

Zebrafish are small striped fish commonly sold in pet stores, and are valued for their hardy nature. For scientists, zebrafish are model organisms that can be used to reveal new clues about all things biological including brain organization, immunology, cancer, and developmental diseases.

Zebrafish eyes, like the rest of their bodies, grow continuously. Each eye grows in a very controlled pattern — new cells are added from a specialized region that encircles the edge of the camera-like part of the eye that senses light (the retina). In this way, the eye grows much like a tree, adding annular rings of new cells that must integrate into the existing tissue. Your eyes are different. They are the same size from the day you’re born until the day you die.

See full details on our publication summary page.

 

An interview with Steve Wilson

Stephen Wilson was recently awarded the Remedios Caro Almela Prize for Research in Developmental Neurobiology. Steve was interviewed to find out about how he started on the road to developmental biology research, how he got interested in the brain, his achievements and future challenges.

See full interview here.

Three new papers reveal how the eye takes shape

The complex choreography of eye formation
Florencia Cavodeassi and Stephen Wilson
October 2009

A gene and a population of cells important for shaping the eye
Gaia Gestri and Steve Wilson
October 2009

A zebrafish model for branchio-oculo-facial syndrome – a condition affecting eye formation
Gaia Gestri and Stephen Wilson
October 2009

Steve Wilson wins the Remedios Caro Almela Prize for research in Developmental Neurobiology

The jury which will award the Remedios Caro Almela Prize IV research in Developmental Neurobiology decided this year to award the prize, worth 18,000 euros, the researcher Stephen Wilson of University College London. This prize is powered by the Chair ‘Remedios Caro Almela’ Miguel Hernandez University (UMH), Elche, attached to the Institute of Neurosciences, joint center of the UMH and the Higher Council for Scientific Research (CSIC).
See website for google translated page

A zebrafish model of the human Oral-facial-digital syndrome

Oral-facial-digital syndrome type 1 (OFD1) is a severe condition that occurs in 1:50,000-250,000 live births. The disease is caused by a defect in a gene called ofd1 that is carried on the X chromosome. We know that Ofd1 protein has a crucial role in development, because XY males inheriting the mutation have no Ofd1 and die before birth, whereas heterozygous XX females (who carry one mutant and one working copy of the gene) are born with several congenital defects: malformation of the face and mouth, abnormalities of the digits and malformation of the central nervous system. OFD1 syndrome often features polycystic kidneys, which is the main cause of death among patients and that can only be treated effectively by kidney transplant. Ofd genes are present in all vertebrate animals and this means that one can potentially model the disease in animals in which it is easier to study why developmental events go wrong than it is in humans. In this study, we elucidated the function of ofd1 during development by depleting Ofd1 protein during zebrafish embryogenesis, using morpholino (Mo) antisense reagents that inhibit the activity of the gene.

See publication summary for full details.

Fgf8 signalling breaks symmetry in the brain

Left-right asymmetry is a universal feature of the central nervous system (CNS) and is fundamental to proper brain function. In this study, we sought to answer a question about which virtually nothing was known: “How is symmetry broken in the vertebrate brain?”

The zebrafish brain shows differences between left and right sides in terms of structure, organization and connectivity of nerve cells (neurons). These features have helped to make the zebrafish a focus for studies of brain asymmetry. We have previously shown that the consistent development of brain asymmetries in one direction (laterality or handedness) is dependent on left-sided activity of a Nodal-family signalling protein. Crucially, if Nodal signalling occurs on both sides of the brain or is absent, brain asymmetries still develop, but are randomised, such that normal brain laterality and reversed brain laterality are equally likely outcomes. Therefore, whilst consistent laterality relies on Nodal signalling, development of an asymmetric brain per se does not, and must be dependent on other signals.

To uncover the signalling pathways required to break symmetry in the brain, we looked for lines of zebrafish carrying genetic mutations that prevent the development of brain asymmetry.

Images of brains of normal (wild-type, WT left) and ace/fgf8 mutant (right) zebrafish in which all cells are labelled with a red nuclear marker (TOPRO-3) and parapineal neurons with an additional green marker (green fluorescent protein). The parapineal neurons are on the left in the wild-type brain but stuck at the middle in the fgf8 mutant.

See publication summary for full details



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