Research: Guiding the optic nerve

3 November 2005

A key molecule guiding the growth of nerve cells that link the eye and the brain has been identified.

In the development of the amphibian visual system, the transcription factor Engrailed-2 is known to set up a gradient of ephrinA ligands that guide the growth of nerves linking the retina and the brain. But Professor Christine Holt (University of Cambridge) and colleagues have now found that it forms a chemical gradient in its own right, attracting axons from one side of the developing eye and repelling axons from the other side.

The optic nerve of each eye is made up of thousands of axons, which, in amphibians and birds, connect to a region of the brain called the optic tectum. (The optic nerve from the right eye makes connections with the left optic tectum, and vice versa.) During the development of the eye, retinal neurons extend axons that grow towards the brain, guided into the correct position by gradients of chemical signals.

The researchers found that retinal growth cones – the growing tips of axons – from one side of the eye (nasal, nearer the nose) were attracted by Engrailed-2, while growth cones from the other side (temporal) were repelled. This corresponds with the arrangement of retinal axons in the optic tectum, where Engrailed-2 is expressed in a gradient from posterior to anterior. They also found that Engrailed-2 enters the growing axon tips and, by activating translation initiation pathways, stimulates the production of new proteins. Transcription factors classically act inside the cells that produce them in animals, so this is the first evidence that a transcription factor protein can influence cell behaviour from the outside.

External links

• Brunet I et al. The transcription factor Engrailed-2 guides retinal axons. Nature 2005;438(7064):94–8.