What Makes Zebrafish so Cool

Last week, a new species of sweeper fish was discovered in the Indian Ocean by a group of marine biologists. The fish has been named Pempheris flavicyla. But it goes by Pebbles for short.

So, fish and science. What can we learn from these goggle-eyed species?

One of the most favoured model organisms in the field of neurobiology has become Danio rerio, also known as the zebrafish.

What Makes Zebrafish so Cool

One of the things that makes the zebrafish a bit of a celebrity within the field of developmental neurobiology is that as an embryo it is transparent. Zebrafish embryos also develop outside of the body, which means that scientists can easily visualise their early stages of development. Their outstanding optical properties enable imaging of their entire intact brains at high resolution by confocal microscopy (see image below), one of a whole host of useful techniques that can help us to understand brain development and neural activity.

Zebrafish have proved particularly useful in studying the developing visual system. We can now label subtypes of retinal cells with fluorescent protein and track them in live zebrafish embryos. This allows scientists to visualise the complex cellular reorganisation that results in the formation of the mature retina.

Zebrafish are also great candidates for optogenetic stimulation…

Confocal microscopy on a zebrafish. Neurons are green. Blue and red are stainings for specific versions of the protein, Tau.

Controlling the Brain with Light

Optogenetics is a technique that allows scientists to control the activity of groups of cells in response to flashes of light.

Optogenetics is pretty incredible as it enables scientists to modulate the activity of different cell populations in living organisms, simply by shining light of certain frequencies at those cells. We can then observe how this affects an organism’s physiology and behaviour. This allows us to better define the roles of different cell types in the growing embryo.

What Does This Mean?

How can zebrafish science give meaning to the way in which we understand human physiology?

Yes, there are some notable differences in the structure and scale of zebrafish brain and human brain, and this means that interpreting studies on the zebrafish requires a greater degree of abstraction than when working with mammalian models. However, zebrafish share 75% of their genome with humans, and the overall organisation of their brain and spinal cord shows many similarities to ours, which means that we can learn some important lessons from this species.

zebra

How an embryo decides to pattern a group of cells and build them into three dimensional structures is central to organ development. Genes important for zebrafish neurodevelopment are usually conserved in mammals and are therefore relevant for understanding normal and abnormal brain development in humans.

Zebrafish are currently being used to research a range of diseases including Parkinson’s disease, Alzheimer’s disease and Huntington’s disease. In addition, because of the anatomical simplicity of their kidneys, zebrafish have become a popular model for studying renal diseases, for example, polycystic kidney disease.  

From Algae to Optogenetics

In order to make neurons sensitive to light, specific gene sequences known as opsins have to be inserted into the animal model being studied. These special sequences must first be extracted from specific microorganisms that contain these light-sensitive proteins.

In 2000, the Kazusa DNA Research Institute in Japan posted thousands of gene sequences for green algae online. Peter Hegemann, a professor at Regensburg University, Berlin, was reviewing these and noticed two long sequences that could be potential candidates for these light-sensitive proteins. In 2005, his team showed that introducing one of these genes into a mammalian neuron could make cells responsive to light with millisecond precision. These proteins were dubbed channelrhodopsin1 and channelrhodpsin2.

algae2
A zoom-in on algae (x400)

Opsins of different types can differ in their light sensitivity and behaviour. For example, directing pulses of blue light onto channelrhodopsin-2 results in neuronal activation, while illuminating another kind of opsin –  halorhodopsin – with yellow light, results in neuronal inhibition.

Halorhodopsin was actually found in a microorganism that is only able to survive in extremely salty conditions. It is found in remote habitats like salt lakes in Kenya and Egypt.

saltlake

Don’t Judge a Pond by Its Algae

One lesson we can take from optogenetics is that even cells from pond serum or harsh Saharan salt lakes can be fundamental to the understanding of human development, physiology and behaviour. It also highlights the value of protecting rare environmental species and the importance of supporting basic scientific research.

Click here to adopt a zebrafish today.

Just kidding. But hopefully now you’ll have a wider appreciation of a fish that you may have never really thought about.

Until next time 🙂

Further reading:

For more information on the neuroanatomy of the developing zebrafish brain, this is a fantastic site: http://zebrafishbrain.org

For more on zebrafish modelling human diseases:

http://155.97.32.9/~bbenham/2510%20Spring%2009/Grunwald-zfdiseasemodnrg08.pdf

http://www.jci.org/articles/view/60434

A brief on optogenetics: http://www.stanford.edu/group/dlab/papers/deisserothsciam2010.pdf

Image credits:

Algae close-up: Captain_wick, Flickr

Algae/lake cross section: Russ MCR, Flickr:  “It may well not be algae”

Zebrafish figure 1: Dominik Paquet, Ludwig-Maximilians-University, Munich, Germany

Zebrafish figure 2: Max Planck Institute for Developmental Biology

*Note: This post has been updated since it was first published.

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