J.H. Horne Lab
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Jack Horne
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Research In the Horne Lab

My lab is interested in identifying the genes that control the development of the brain.  Development of the brain requires that neurons (nerve cells) acquire their own, very unique shape such that they can connect to distant neurons, and receive connections from many, sometimes thousands, of other neurons.  In order to form these complex networks of neuron-to-neuron connections, these cells extend complex, branched, finger-like extensions called axons and dendrites, which in their final structure frequently resemble the roots or branches of a tree.  The axon branches are the voice of the neurons, sending signals to multiple target neurons, and the dendrite roots are the ears of the neurons, sensing signals from many other neurons.  The job of the neuron is to integrate the many signals it receives, and then determine what type of signal to send on to downstream target neurons.  Thus, which upstream and downstream targets an individual neuron connects to is determined by the complex, branched structure of its axons and dendrites.  In the end, in a fully functioning brain, the very unique shape of a particular neuron is a reflections of its functional connections, and to effectively function each neuron must acquire its characteristic shape.

Cerebrum 5X
In my lab, we use zebrafish – the small aquarium fish known as Danio rerio to aficionados – as a model system to actually visualize changes in shape of neurons as the early brain develops. Zebrafish embryos are essentially transparent, making them very useful for microscopy studies that visualize cells in the live animal (called in vivo imaging). We can image the shapes of developing neurons by incorporating a fluorescent protein into the cells early in development.
Cerebrum 20X
We then follow changes in cell shape or structure over time using a fluorescence microscope. One of the great advantages of this method is that it allows you to see the structure of developing neurons in live embryos. You can see examples of fluorescent brains in live embryos scattered about our website (click here for a video of fluorescent neurons). Fortunately, the basic structure of the brain is conserved across vertebrates, and in particular, the mechanisms that control shape changes of individual neurons seem to be quite similar. Thus, genes that we identify as being necessary or important for development of the zebrafish nervous system are likely to have mammalian, and even human, counterparts.
Red Blue Midbrain
We are currently characterizing a technique that we can use to deliver the gene for the fluorescent protein into developing neurons at specific stages of development. This technique, called in vivo electroporation, uses very brief electric pulses to incorporate the DNA expression plasmids across the plasma membrane and into the neurons. The advantages of this method are: (1) it can done at any stage of development; (2) it does not harm the embryos or adversely affect development; and (3)
Red Neurons
it can be spatially-targeted to large regions of the developing brain or to a few (or even one) specific types of neurons. This allows us to examine whichever developmental process we’re interested in. In addition, this same technique can be used to deliver gene loss-of-function reagents – which knockout the function of a specific gene – such as RNA interference reagents or antisense morpholino oligonucleotides. Thus, we can examine the characteristic shape changes that a particular neuron undergoes during normal development, and then knockout a specific gene and determine if that leads to altered shape changes. This will allow us to identify which genes are important for specific neuronal shapes, and we can assess this for development of many different brain regions or stages. See “Members and Collaborators” to see whose actually doing the work.

 

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