The thin, tail-like projections known as cilia that extend from certain types of cell are found in a wide variety of organisms. The single-celled Paramecium, for example, uses cilia to propel itself through water. In humans, cilia in the lining of the trachea sweep mucus and dirt out of the lungs, and in the fallopian tubes they move the ovum from the ovary to the uterus. But in all instances the cilia always point in a specific direction relative to the organ they serve.

Chris Kintner, a molecular neurobiologist at the Salk Institute for Biological Sciences in La Jolla, California, and his team reveal on page 97 how they believe this 'pattern' is established.

“This question came out of the blue for us,” says Kintner. About two years ago, his group was investigating the development of ciliated cells in the skin of the African clawed frog Xenopus laevis, a favourite model organism among developmental biologists. They noticed something strange about Xenopus embryos growing in culture. The embryos tended to float at the bottom of the dish because the cilia on the skin cells produced a flow oriented along the embryonic axis from head to tail.

Intrigued by the observation, Kintner and his postdoc Brian Mitchell searched the literature for other examples of ciliary flow in a particular direction along the axis of an organ — and they found plenty of them. “It was remarkable to me that so many people had reported the phenomenon in different systems but so little was known about how cilia become directed,” Kintner says.

Inspired by classic studies done in the 1940s and 1950s, the team removed patches of skin from Xenopus embryos as they developed, to check the cilia's orientation. Recruiting the help of Richard Jacobs, an electron microscopist also at the Salk, the researchers took a close-up look at the basal foot, the structure from which a cilium grows. “The basal foot acted as a little compass to reveal cilium polarity,” says Kintner.

They found that when cilia first form on cells in Xenopus skin, they all point towards the tail. But this initial patterning is not very precise. The cilia become better organized and established as more cilia begin beating in the same direction. Kintner suspected that the flow created by the beating cilia had something to do with the refinement step.

To test this idea, the team exposed Xenopus skin to flow from different directions. “We tried to do all kinds of crazy things to create flow,” says Kintner. In the end, he sought the help of Shu Chien, a bioengineer at the nearby University of California, San Diego, who had developed a system of flow chambers that could replicate physiological flow. Using Chien's system, Kintner's group showed that imposing flow in a different direction from that of the cilia caused them to reorient themselves.

Based on these results, Kintner proposed a model in which the initial patterning step in Xenopus gives cilia a posterior 'bias', allowing ciliated cells to produce flow in one direction. This flow, in turn, acts as a positive feedback loop: as cilia produce flow, they sense it and modulate their orientation to optimize it. Kintner says the work has given the team a starting point for investigating the molecular mechanisms involved in these pathways.