Monday, 30 April 2012

A neuronal growth cone sets out on its journey

Spring 2012 Newsletter of the Faculty of Life Sciences (The University of Manchester)

I wanted to show my photo - “A neuronal growth cone sets out on its journey” - which is appearing on the cover of our Faculty of Life Sciences newsletter. It is of a nerve cell taken from a fruit fly (Drosophila melanogaster) embryo and grown on a glass cover slip for easy visualisation. The cell body is at the bottom, with an axon growing from it and ending in the growth cone (top). 

 Left: Precise wiring of the nervous system. Right: The 1901 network of submarine telegraph cables

On the cover slip the growth cone is setting out on a journey with no end, but back in the developing fruit fly it would have had a specific destination, be it another nerve cell, a muscle or a gland. The problem faced is somewhat akin to that of laying submarine communications cables. After several pioneering attempts to lay transatlantic cables failed, the SS Great Eastern finally made a successful connection  in the 1860s. Much like nerves in the body, these cables allowed information to be passed between specific locations, huge distances apart (distances spanned by nerves are great even in the fruit fly, when considered relative to the length of an average cell). At the growing nerve end, the growth cone’s role can be thought of as that of the cable laying ship; both set out with a predetermined target location, with which they must establish a physical communication link. Both must move forward, laying behind cable or axon as they go, and both must be able to steer in response to information concerning their location (in the case of the growth cone this information takes the form of chemical signals that it encounters in different regions of the developing embryo), and so come to their journey's end in the right place. In this way nerve cells connect up to form the wiring which controls the fly’s behaviour.

My photo shows the two main components of the cytoskeleton inside the nerve cell (these are essentially filaments with structural roles – acting like scaffolding to give the cell rigidity, and as the rails for transporting molecules around the cell. They are also highly dynamic and can be rearranged to drive changes for example in the cell's shape). The two components are actin filaments in pink and microtubules in green.

During my last few years in the Prokop lab I have been studying how these cytoskeletal components (particularly the microtubules) drive the forward growth of the axon. It may sound surprising but what we learn about these processes in the fruit fly, is relevant for understanding our own nervous systems. This is because there are remarkable similarities between humans and fruit flies, both in our genes (for example 74% of human genes involved in disease have known counterparts in the fruit fly) and at the level of several organ systems (for example the heart; Drosophila tinman mutants fail to grow a heart (as in The Wizard of Oz where the tinman has no heart), and the mammalian version of the tinman gene has since been shown to serve the same function). Importantly the nervous system is another organ system which shows great similarity between Drosophila and ourselves. Drosophila has therefore played a pioneering role, for example in discovering genes and mechanisms involved in guiding the growth cone, which have been found to play similar functions in mammals. This similarity is also illustrated by the similar organisation of the cytoskeleton seen in my photo of a fly neuron, when compared to a mouse neuron.

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