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Scientists identify gene crucial to normal development of lungs and brain

master gene

The Salk researchers discovered the master gene that tells cells to develop multiple hair-like cilia, such as those seen in pink in this false-colored electron microscope image of the surface of a frog embryo.

Image courtesy of the Salk Institute for Biological Studies; Chris Kintner, Molecular Neurobiology Laboratory, and Matthew Joens and James Fitzpatrick, Waitt Advanced Biophotonics Center

Most cells in our body project a single, nonmoving cilium—a tiny hairlike structure—used as a minute antenna for detecting chemical and physical stimuli. But certain specialized tissues require cells with 100 to 200 moving cilia that beat in concert to move fluids through the body. 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 to prevent infections.

In research reported in Nature Cell Biology, a team in the lab of Christopher R. Kintner has identified a gene that tells cells to develop multiple cilia. In a previous study, Kintner and his group identified a protein, FoxJ1, that pro- moted the formation of a single moving cilium. What remained unclear was how certain cells activate FoxJ1 in a way that leads to the forma- tion of hundreds of motile cilia per cell. In their new study, Kintner and his collaborators worked with mice and African clawed frogs to identify a gene that produces a second protein, which they dubbed "multicilin," that tells cells to develop multiple cilia. When cells are exposed to multi- cilin, 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.

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 damaged cells with new ciliated cells, but first scientists need to know how to guide stem cells along a pathway into multiciliate cells.

"Our findings suggest that multicilin could be central to differentiating stem cells into replace- ment cells," Kintner says. "It's a necessary step in developing therapies."