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Cilia guide neuronal migration in developing brain
Date:11/12/2012

cle control, breathing problems, and sometimes intellectual disability.

Caspary's laboratory has been studying Arl13b, a gene mutated in Joubert syndrome. Mutations in Arl13b lead to cilia that are short and stubby.

"It's a useful tool for studying the role of cilia in development, because it doesn't take a sledgehammer to the entire structure," Caspary says.

Exactly how Arl13b contributes to the function of cilia is unclear it appears to be involved in protein transport needed for building cilia because when it is hyperactivated, cilia are longer.

Caspary's and Anton's laboratories teamed up to look at neuronal migration in mouse embryos where Arl13b was deleted, but only in some types of neurons. "Interneurons" form connections between other neurons and do not connect to muscles or sensory organs. They observed that when Arl13b was deleted in interneurons, those cells did not migrate properly through the developing cortex of the brain.

The team probed cilia by using mice that produced a red fluorescent protein within cilia. Slices of embryonic brain were examined with a confocal microscope, under conditions where the cells stay alive and continue moving for several hours.

The scientists could see the interneurons migrating in spurts, with the cilia tending to extend and move "like basketball players' arms" when the cells paused. In the Arl13b deleted mice, the cilia did not extend as much and often could be seen only as red dots. Reintroducing Arl13b could rescue these defects, while a form of Arl13b found in Joubert syndrome patients could not.

How defects in cilia contribute to Joubert syndrome is complex; cilia are needed for Hedgehog signaling, machinery that controls embryonic patterning. Caspary says the neuron migration problem may explain the intellectual disability aspect, while Hedgehog defects may explain impaired development of the cerebellum and brainstem.


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Contact: Quinn Eastman
qeastma@emory.edu
404-727-7829
Emory University
Source:Eurekalert

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