'Rich' connection enables neurons to find specific targets

These connections between neurons are often specific.

In the fruit fly (Drosophila melanogaster), for example, a defect may cause a photoreceptor in the eye to “see” the light and fire the neuron but the signal cannot transmit the information to the next neuron. Somehow, the link between neuron and its target has been lost, and without this link, the flies are blind.

In a report in the current issue of the journal Neuron, scientists at Baylor College of Medicine and the Jan and Dan Duncan Neurological Institute at Texas Children’s Hospital have identified a novel gene called rich (ric1 homologue) that acts to ensure that the specificity of certain neurons for their target is established properly.

Novel mechanism

When the rich protein is mutated, Dr. Hugo Bellen, professor of molecular and human genetics at BCM and his colleague, Dr. Chao Tong believe that it can no longer activate another protein called Rab6. Rab6 is involved in the transport of N-Cadherin, a cell-adhesion molecule important in the formation of synapses.

What is different about this is the specificity, said Bellen, who is also a professor of neuroscience, a Howard Hughes Medical Institute investigator and director of the Program in Developmental Biology.

“Mutations in rich and Rab6 only affect a subset of neurons,” he said. “Proteins like Rab6 are thought to be widely expressed and to affect many cells. You would expect developmental effects everywhere, but only a small subset of proteins in a subpopulation of neurons are affected in this case.”

“This is a novel mechanism by which you can regulate in an unanticipated fashion how a specific neuron connects to another neuron,” said Bellen.

Neural network important

“How are our brains wired?” said Bellen. “If you wire a brain, you have to connect billions of neurons. How do you achieve the necessary specificity? Many different mechanisms are involved and much is achieved during the development of the organism.”

“This work reveals another way to do that – through the control of trafficking of a cell adhesion molecule. It is a way to tell specific neurons how to make a connection,” he said. “It is the neural network that is important – not the individual neurons.”

Others who took part in this work include first author Tong, who is now an assistant professor at Zhejiang University in Hangzhou, China; Dr. Tomoko Ohyama, Dr. An-Chi Tien, Dr. Akhila Rajan and Claire M. Haueter, all of BCM.

Funding for this work came from the National Institute of Neurological Disorders and Stroke, the Intellectual and Developmental Disabilities Research Center at BCM and the Howard Hughes Medical Institute.

Bellen holds the March of Dimes Chair in Developmental Biology.

For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.

   Glenna [email protected]