Axon guidance in Drosophila

Published on September 29, 2008 Reviewed on September 25, 2017   34 min

Other Talks in the Therapeutic Area: Neurology

I'm J.B Thomas from the Salk Institute. And in this lecture I'll be talking about axon guidance in Drosophila. I'll review the impact that studies in Drosophila have had on our understanding of how axons are guided to their synaptic target cells. Thus forming the circuits that make up the nervous system. And in doing so I hope to give some idea of how Drosophila has been capitalized on as a genetic model system to advance the field.
The axon guidance field traces its roots to the great anatomist Ramon y Cajal who in the late 19th century first hypothesized that the basic unit of the nervous system is the single neuron. And this led him to think about how neurons might be assembled during development. And the question he posed in one of his early works is as much the guiding question of the field today as it was over 100 years ago. He wrote, "wherein lies that marvelous power which enables the nerve fibers from very distant cells to make contact directly with certain other nerve cells, without going astray or taking a roundabout course?" In essence, he was asking how the nervous system wires itself up. And as he illustrated in many drawings, Cajal went on to propose that a way a neuron grows is via the growth cone at the tip of its axon. And that the growth cone is endowed with the ability to sense chemical signals. And work over the past two decades, much of it on Drosophila has helped to elucidate the molecular basis effects on guidance and continues to confirm how truly visionary Cajal's work was.
In terms of the Drosophila nervous system, I'd like to start by showing a section through an adult fly's brain. Just to give you an indication of how complicated a tissue it actually is. This section was stained using a technique similar to that used by Cajal over a century ago. There are over 100,000 neurons in the brain, only some of which of course are visible in this section, and their synaptically connected with great precision. The neuronal cell bodies lie near the periphery. They're bilaterally symmetric around the midline. Essentially everything else in the section is composed of axonal projections. And at first glance it looks a bit disorganized. But upon further analysis, you can see that there's a very fine and regular structure in which neurons project their axons along specific pathways to reach in synapse with their targets. For example, this hypothetical pink neuron might project this axe on across the midline from one side to the other, in order to synapse with its target cells. And the homologous cell on the other side would do the same in mirror image. But what I'll be talking about is how during development axons are guided to their specific target destinations, allowing them to synapse with their appropriate partners. We'll be examining these events in the embryo where there are far fewer cells in the architecture is much simpler than it is here in the adult.