Molecular Scaffold Guides Connections Between Brain Cells

Central to the wiring architecture of the cerebellum are the so-called Purkinje cells, a type of neuron that deploys a bushy array of fibers called dendrites that extend through layers of cerebellar territory. The dendrites gather signals from many other neurons in the cerebellum and send signals to other parts of the body.

Distinctive wiring patterns are unmistakable in the cerebellum, a brain region best known for controlling movement, in both mice and people. Compared to regions involved in more sophisticated functions like vision and thought, "the cerebellum is an easier place to start, because of its very organized architecture,” said Z. Josh Huang, Ph.D., a professor at Cold Spring Harbor Laboratory (CSHL; Cold Spring harbor, NY, USA), who led the team that identified molecules guiding this highly specific neuronal targeting in the developing brains of mice.

A few years ago, Dr. Huang's team established that a protein from the immunoglobulin family directs one group of cerebellar neurons to connect with a specific part of Purkinje cells. Immunoglobulin proteins are best known for acting as antibodies in the immune system, where they take on myriad forms to attack new invaders. Here, however, they were observed to be involved in the wiring of the brain.

Dr. Huang's team traced the subcellular targeting of a different set of cerebellar neurons called stellate cells, which make numerous connections to the dendritic "bush” emanating from clumps of Purkinje cells. Unlike the cells they had studied previously, however, these neurons need help to form synapses. The nonsignaling brain cells, known as glia, form a kind of scaffold directing the growth of nerve fibers and their connections between specific types of neurons.

This study of how the brain develops its complex wiring, has given scientists hope that they will be able to clarify what goes wrong in disorders such as autism.

The study was reported in the April 2008 journal PLoS Biology.


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