Directional ciliary beats across epithelia require Ccdc57-mediated coupling between axonemal orientation and basal body polarity.

Motile cilia unify their axonemal orientations (AOs), or beat directions, across epithelia to drive liquid flows. This planar polarity results from cytoskeleton-driven swiveling of basal foot (BF), a basal body (BB) appendage coincident with the AO, in response to regulatory cues. How and when the BF-AO relationship is established, however, are unaddressed. Here, we show that the BF-AO coupling occurs during rotational polarizations of BBs and requires Ccdc57. Ccdc57 localizes on BBs as a rotationally-asymmetric punctum, which polarizes away from the BF in BBs having achieved the rotational polarity to probably fix the BF-AO relationship. Consistently, Ccdc57-deficient ependymal multicilia lack the BF-AO coupling and display directional beats at only single cell level. Ccdc57 -/- tracheal multicilia also fail to fully align their BFs. Furthermore, Ccdc57 -/- mice manifest severe hydrocephalus, due to impaired cerebrospinal fluid flow, and high mortality. These findings unravel mechanisms governing the planar polarity of epithelial motile cilia.