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November 6, 2012--------News Archive Return to: News Alerts


Cilia on the surface of a developing mouse embryo. The cilia were colored
red
(artificially) after this image was produced via electron microscopy.
The smaller protuberances are microvilli.



WHO Child Growth Charts

       

Cilia Guide Neuron Migration in Developing Brain

A new study demonstrates cilia guiding the migration of neurons in the embryonic brain. Cilia are tiny hair-like structures on the surfaces of cells, but here they are acting more like radio antennae

In developing mouse embryos, researchers were able to see cilia extending and retracting as neurons migrate. The cilia appear to be receiving signals needed for neurons to find their places.

Genetic mutations cause the neurodevelopmental disorder Joubert syndrome which affects the development of the cerebellum and brain stem, leading to lack of muscle control, breathing problems, and sometimes intellectual disability. Joubert syndrome also seems to reflect interference within the migratory functions of cilia. The latest findings suggest that problems with neuron migration may explain some aspects of Joubert syndrome patients' symptoms.

Study results were published in the November 13, 2012 issue of the journal Developmental Cell.


"The most surprising thing was
how dynamic the cilia are
.
As interneurons migrate into
the developing cerebral cortex,
they move in steps. When they pause,
we could see the cilia extending,
as if the interneurons are trying
to figure out where to go next."

Tamara Caspary, PhD
assistant professor, human genetics
Emory University School of Medicine


The published paper is the result of a collaboration between Caspary's laboratory and that of Eva Anton, PhD, professor of cell and molecular physiology at University of North Carolina School of Medicine. First author Holden Higginbotham, formerly a postdoc in Anton's laboratory, is now a faculty member at Brigham Young University in Idaho.

Motile cilia can be found on a paramecium, in our trachea, and on our reproductive organs. In contrast, primary (non-motile) cilia can be found on almost every cell in the human body, with each cell having just one cilia. Ciliopathies are a class of genetic disorders involving defects in cilia, and include kidney and eye diseases as well as Joubert syndrome.

Caspary's laboratory has been studying gene Arl13b, where a mutation in Arl13b leads 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. However, it appears to be involved in protein transport needed for building cilia. When it is hyperactivated, cilia grow longer.

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


How defects in cilia contribute to Joubert syndrome
is complex; cilia are needed for Hedgehog signaling,
machinery that controls embryonic patterning.

Caspary believes the neuron migration problem may
explain the intellectual disability aspect of Joubert's,
while Hedgehog defects may explain impaired
development of the cerebellum and brainstem.


Original article: http://news.emory.edu/stories/2012/11/cilia_in_developing_brain/index.html