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Watching the Developing Brain, Scientists Glean Clues on Neurological Disorder

15.11.2012
As the brain develops, each neuron must find its way to precisely the right spot to weave the intricate network of links the brain needs to function. Like the wiring in a computer, a few misplaced connections can throw off functioning for an entire segment of the brain.

A new study by researchers at the University of North Carolina School of Medicine reveals how some nerve cells, called interneurons, navigate during the development of the cerebral cortex. Mutations in a key gene behind this navigation system underlie a rare neurological disorder called Joubert syndrome; a condition linked with autism spectrum disorders and brain structure malformations.


Eva Anton Lab, UNC School of Medicine

The left panel shows normal neuronal cell organization (red and green). Organization is lost when Arl13b gene is deleted (right panel).

The study was published online on Nov. 12, 2012 by the journal Developmental Cell.

“We were trying to understand how neurons get to the right place at the right time during brain development,” said senior study author Eva Anton, PhD, a professor in the UNC Neuroscience Center and the Department of Cell Biology and Physiology at the UNC School of Medicine.

To do that, the UNC researchers and their collaborator, Dr. Tamara Caspary, at Emory University tracked brain development in mice with and without a gene called Arl13b. They found that the gene, when functioning normally, allows interneurons to use an appendage called the primary cilium as a sensor.

These appendages are found on many types of cells, but scientists did not previously know what they were doing on developing neurons.

“We found that primary cilia play an important role in guiding neurons to their appropriate places during development so that the neurons can wire up appropriately later on,” said Anton. “It’s like an antenna that allows the neuron to read the signals that are out there and navigate to the right target location.”

Neurons in mice without the Arl13b gene or expressing mutant Arl13b found in Joubert syndrome patients essentially had a broken antenna, causing the cells to get lost on the way to their destinations.

Variants of the Arl13b gene are known to cause Joubert syndrome, which is characterized by brain malformations, abnormal eye and tongue movements, low muscle tone and mental retardation. This is one of the first studies to uncover how mutations of this gene actually disrupt brain development.

“Ultimately, if you’re going to come up with therapeutic solutions, it’s important to understand the biology of the disease,” said Anton. “This contributes to our understanding of the biological processes that are disrupted in Joubert syndrome patients.”

Co-authors include Holden Higginbotham, Tae-Yeon Eom, Amelia Bachleda, Joshua Hirt, Vladimir Gukassyana and Corey Cusack from UNC, Laura E. Mariani and Tamara Caspary of Emory University, and Cary Lai of Indiana University, Bloomington.

Les Lang | Newswise Science News
Further information:
http://www.med.unc.edu

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