Self-guiding axons map out the brain

Scientists at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London have demonstrated for the first time that target-independent communication between axons is essential for the correct wiring in the developing brain.

The formation of specific connections between nerve cells is essential for brain development. Nerve cells in the brain send out projections called axons to connect and communicate with target cells. This process is complex and controlled by numerous different mechanisms. Previously, scientists thought that these target cells contained the information to guide axons to their correct destination. This study, published in the journal Neuron, showed that the axons themselves contain the essential tools required for guidance to the correct destination.

The researchers, based at the Medical Research Council (MRC) Centre for Developmental Neurobiology at the IoPPN, discovered that a molecule called ephrinA5 was indispensable for repellent axon-axon interactions. They found that it prevents the intermingling of axons from different types of nerve cells, thus allowing the correct development of nerve connections.

In order to study axon-axon interactions, the researchers looked specifically at the connections that occur between the eye and the first relay station for visual signals in the brain called the tectum. Using an animal model system, the researchers studied the consequences of removing the molecule EphrinA5 only from axons. Deleting this molecule caused nerve cells from the eye to form connections with the wrong cells and no longer communicated visual signals to their target cells in the tectum.

Establishing connections between nerve cells from the retina and the tectum can be used as a model for processing information from the outside world, including sound, smell, taste and touch; therefore these findings are more widely applicable to axon communication across all regions of the brain.

Professor Uwe Drescher, from the MRC Centre for Developmental Neurobiology at the IoPPN, King’s College London, who lead the research, says: “The nerve cell connections between the retina and the tectum have been studied for decades. Our research has uncovered a new fundamental feature of axon guidance – that axons not only communicate with target cells, but also communicate with other axons to correctly set-up connections. This finding has important consequences for our understanding of brain development and might ultimately lead to a better understanding of neurodevelopmental disorders such as autism. “

Paper reference: Philipp Suetterlin and Uwe Drescher “Target-independent ephrinA5/ephA-mediated axon-axon repulsion as a novel element in retino-collicular mapping” published in Neuron DOI: http://dx.doi.org/10.1016/j.neuron.2014.09.023