David Ginty

David Ginty of
Neuroscience
on the challenges in understanding
nervous system development:

What are some major challenges to understanding neural circuitry?

GINTY: One huge, fundamental challenge is to identify the individual components of the circuits themselves. For somatosensory neurons, we don’t even yet know the identity of all of the nerve cells that make up particular circuits, such as those that mediate pain sensations or touch. Another challenge is to identify the molecular cues and their cell surface receptors that instruct the axonal projections of individual neurons to grow toward and connect to their appropriate targets. We’re also trying to understand how these cues transmit their signal to the interior of the axon to make it grow or stop growing and whether some of the cues can be used or manipulated to aid in the regeneration or repair of injured nerve cells.

Where do these guidance cues come from?

GINTY: We recently discovered that some endothelins, previously implicated in cardiovascular control, can guide sympathetic neurons in the head toward certain blood vessels, which the axons then use as roadways to travel along as they grow into distinct target fields such as the salivary gland. In this case, the cues are made by blood vessels. Since endothelins are made in many other places in the developing nervous system, we speculate that they are important for establishing connections made by many different classes of neurons.

What types of tools do you use for studying nervous system development?

GINTY: Comparative genomics has been very useful—axon growth and guidance cues are found in all organisms that contain a nervous system. And, amazingly, the functions of these factors are conserved from invertebrates to vertebrates. The whole field has taken many lessons from our colleagues who discover new cues in simpler systems such as flies and worms, to identify the mammalian counterparts, which have taught us a lot about how more complex nervous systems develop. For example, my colleague Alex Kolodkin discovered the first semaphorin in grasshoppers, and it turns out that members of the semaphorin family are enormously important for development of the mammalian brain and spinal cord.

Where is the axon guidance field heading?

GINTY: We still have a long way to go to identify all the cues that control axon guidance and growth, both in the brain and the periphery. In addition to identifying the cues, we also need to figure out where and when they’re made, how they work and, importantly, how neural circuit assembly is affected when these cues are missing. We’re still a long way off from understanding how the billions of nerve cells in the mammalian brain are wired up into circuits that enable sensory and motor behavior, learning and memory, and consciousness.

David Ginty on development of sensory neurons: