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Broken ‘antenna’ can lead to lost neurons

UNC-CHAPEL HILL / EMORY (US) — A new study with mice shows how nerve cells, called interneurons, use a “sensor” to find the right destination during the cerebral cortex’s development.

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.

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.

“We were trying to understand how neurons get to the right place at the right time during brain development,” says senior study author Eva Anton, a professor in the University of North Carolina Neuroscience Center and the department of cell biology and physiology at the UNC School of Medicine.

To do that, the researchers and their collaborator, Tamara Caspary of 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,” says 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. The findings are published in the journal Developmental Cell.

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

Additional co-authors contributed from UNC, Emory University, and Indiana University, Bloomington.

Source: UNC-Chapel Hill

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