Motile cilia, tiny hairlike structures, sweep mucus and dirt out of our lungs and in females propel the egg from the ovary through the Fallopian tube into the uterus. Although a lot is known about the structural details of cilia—an array of microtubules arranged in nine doublets around a central pair is anchored through the so-called basal body inside the cell—how cilia form in epithelial cells and how they coordinate the direction of their stroke along a common polar plane is far from clear.

Tracking the orientation of hundreds of cilia in Xenopus larvae, whose skin is covered with multiciliated cells, Kintner and his team found that during early embryonic development, cilia point more or less in the general direction of the body's back end and start creating a weak flow. During the following refinement phase, all cilia get in line and trim their sails to the prevailing winds. To learn more about the underlying molecular mechanisms, Kintner initiated an analysis of the planar cell polarity (PCP) pathway, which is widely used as a mechanism to orient structures within cells and tissues. He started by eliminating a cytoskeletal anchor protein, Dishevelled, a known PCP component in frog cells that normally carry cilia. Without Dishevelled, the cells failed to develop proper cilia.

The cilia defect in the Dishevelled mutant was very similar to the phenotype Kintner and his team had observed when they eliminated a genetic switch called FoxJ1. Just as in mice lacking FoxJ1, ciliated cells did not form cilia, apparently because basal bodies failed to dock at the cell surface where cilia outgrowth normally occurs. When the researchers expressed FoxJ1 in cells that are normally not ciliated, basal bodies formed in these cells, docked at the surface, and sprouted cilia because of FoxJ1. From these and other observations, Kintner concluded that FoxJ1 functions as a master regulator of ciliogenesis, and he is planning to study the genes activated by FoxJ1 in more detail. Identifying the components involved in cilia-specific functions and in the molecular mechanisms underlying the various ciliopathies is likely to facilitate the development of novel therapeutic strategies.