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Source:  
Medical College of Georgia

http://www.sciencedaily.com/releases/2005/10/051025072807.htm


Date:  
2005-10-25





Lipids Play Important Role In Nervous System Development

 

Blocking a signaling lipid can keep nerves from developing the arm-like 
extensions they need to wire the body and may even cause neurons to die, 
researchers have found.

 


 
Dr. Wen-Cheng Xiong, developmental neurobiologist, and Dr. David J. Kozlowski, 
developmental geneticist and director of the MCG Transgenic Zebrafish Core 
Laboratory. (Photo by Phil Jones)
  


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The researchers hope this piece of the puzzle of how the central nervous 
system develops in the first place will one day help them repair loss from 
injury or disease.

 

It’s already helped them understand the ailments of a spontaneous mouse mutant 
that has about 20 percent function of the protein that helps the lipid get to 
the cell surface so it can help axons grow, says Dr. Wen-Cheng Xiong, 
developmental neurobiologist and corresponding author on the study published 
in the November issue of Nature Cell Biology.

 

The mutant mouse is small and has motor neuron degeneration, with tremors, 
short limbs and a short life, she says. Before this new work, what the 
blocked lipid transfer protein regulated was still a mystery.

 

The lipids in question aren’t those measured during an annual physical exam, 
rather those that help give shape and function to units within cells such as 
the nucleus and cell powerhouse, or mitochondria, she says.

 

“Traditionally people didn’t think these lipids were regulated. They thought 
they were just there,” says Dr. Xiong. “But what we found is this particular 
lipid is regulated; it’s like a signaling molecule. Especially during axon 
growth, the dynamic regulation is more dramatic.”

 

She and her colleagues found the lipid is transferred to the cell surface at 
just the right time and place by phosphatidylinositol transfer protein-a, 
which humans also have. It’s been known that many proteins can be regulated, 
especially signaling proteins that enable intracellular chatter. “Now we have 
found this protein regulates lipids and lipids also travel,” Dr. Xiong says.

 

The mouse mutant is a clear example of what can happen when the lipids don’t 
travel. The researchers also studied a similar mutant chick embryo that had 
reduced axon growth. For this paper, they added the zebrafish embryo, which 
forms most of its major organs within the first 24 hours and remains 
transparent for the first few days of life, to further document the role of 
these regulated lipids and their transfer protein.

 

When they injected an agent that blocks expression of a related lipid 
transport protein, the next they could see the impact on axon growth and 
neuron survival, says Dr. David J. Kozlowski, developmental geneticist and 
director of the MCG Transgenic Zebrafish Core Laboratory. They looked at 
different levels of suppression, finding the greater the suppression, the 
greater the resulting defect. “It shows this protein is critical for 
development,” Dr. Xiong says of repeated findings.

 

Next they’ll use a version of the transgenic zebrafish that will enable them 
to watch axon development – or lack of it – in live embryos and in real time, 
Dr. Kozlowski says.

 

They also want to look at what happens to the lipid activity in an injury 
model. They already know some signaling proteins are disturbed.

 

MCG contributors included the laboratories of Drs. Xiong and Kozlowski as well 
as Dr. Lin Mei, program chief in Developmental Neurobiology and Georgia 
Research Alliance Eminent Scholar in Neuroscience.

 

Collaborating institutions include the University of Alabama at Birmingham; 
the Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai 
Institutes for Biological Sciences, Chinese Academy of Sciences; Howard 
Hughes Medical Institute; and the Jackson Laboratory in Bar Harbor, Maine.

 

The work was supported by the National Institutes of Health.

 

Editor's Note: The original news release can be found here.

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