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Scientists identify gene crucial to normal development of lungs and brain
Date:1/12/2012

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These cells aid in pushing cerebrospinal fluid through the brain and spinal cord, helping to circulate and replenish this fluid. In the respiratory system, the cilia push mucus that traps dust, pathogens and other foreign matter from the lung up into the trachea, helping prevent infections.

In a previous study, published in Nature Genetics, Kintner and Stubbs identified a protein, FoxJ1, that promoted the formation of a single moving cilium. What remained unclear is how certain cells activate FoxJ1 in a way that leads to the formation of hundreds of motile cilia per cell.

In their new study, Kintner and his collaborators identified a gene that produces a second protein, which they dubbed "multicilin," that tells cells to develop multiple cilia. When cells are exposed to multicilin, their genetic mechanisms for developing multiple cilia are activated. In a developing embryo, the protein instructs certain stem cells that will line the lungs, kidney and skin to develop into multiciliate cells.

When the researchers inhibited multicilin's action, the frogs' skin and kidney failed to form multiciliate cells. The scientists also found that multicilin is both necessary and sufficient to instruct the development of multiple cilia in cells that line the airways of mice.

"This means that multicilin directs the development of these cells in a number of different organs," Kintner says. "How multiciliate cells develop had been a mystery, but this fills in a big piece of the puzzle."

Kintner notes that patients with respiratory diseases such as chronic asthma, emphysema and cystic fibrosis often suffer from lung infections, which may result from damage to the ciliated cells that move protective mucus out of the airways. In the future, stem cell therapies might replace those damage cells with new ciliated cells, but first scientists need to know how to guide stem cells along a pathway into multiciliate cells.

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Contact: Andy Hoang
ahoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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