科学家发现影响肺、脑生长的基因

Scientists at the Salk Institute for Biological Studies have identified a gene¹ that tells cells to develop multiple cilia（纤毛，睫毛） , tiny hair-like structures that move fluids through the lungs and brain. The finding may help scientists generate new therapies that use stem cells to replace damaged tissues in the lung and other organs. "Cells with multiple cilia play a number of important roles, including moving fluids through the respiratory（呼吸的） tract², brain and spinal³ cord," says Christopher R. Kintner, a professor in Salk's Molecular⁴ Neurobiology Laboratory, who led the research. "Knowing the gene that instructs cells to develop multiple cilia helps us understand how we might coax⁵（哄骗） stem cells into developing into this type of cell, which we could then use to repair damaged tissue."

The findings of the research, which was supported by the National Institutes of Health and Salk's Innovation Grants Program, were published in the January 8 online issue of Nature Cell Biology.

Kintner and his collaborator⁶, Jennifer Stubbs, a scientist now at Pathway Genomics, a San Diego biotech company, along with Eszter Vladar, a postdoctoral fellow in the laboratory of Jeffery Axelrod, at the Stanford University School of Medicine, made their discovery by initially⁷ studying the embryos⁹ of African clawed frogs (Xenopus laevis).

Multiciliate cells form on the outside of the embryos, making them easy to study, and the genetic¹⁰ mechanisms¹¹ that direct the frog cells to develop multiple cilia are likely similar to those of humans.

Humans and other organisms inherited cilia from our single-celled primordial¹²（原始的） ancestors that used these beating structures as a form of propulsion. Most cells in our body project a single, non-moving cilium used as a tiny antenna¹³ for detecting chemical and physical stimuli¹⁴. But certain specialized¹⁵ 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, helping¹⁶ to circulate and replenish¹⁷ 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（气管，导管） , 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 activate¹⁸ 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 dubbed¹⁹ "multicilin," that tells cells to develop multiple cilia. When cells are exposed to multicilin, their genetic mechanisms for developing multiple cilia are activated²⁰. In a developing embryo⁸, the protein instructs certain stem cells that will line the lungs, kidney and skin to develop into multiciliate cells.

When the researchers inhibited²¹ 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 airways²² of mice.