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Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11170-E11179. doi: 10.1073/pnas.1716522115. Epub 2017 Dec 11.

Daple coordinates organ-wide and cell-intrinsic polarity to pattern inner-ear hair bundles.

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Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065.
Laboratory of Sensory Neuroscience, The Rockefeller University, New York, NY 10065.
The Jackson Laboratory, Bar Harbor, ME 04609
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065;


The establishment of planar polarization by mammalian cells necessitates the integration of diverse signaling pathways. In the inner ear, at least two systems regulate the planar polarity of sensory hair bundles. The core planar cell polarity (PCP) proteins coordinate the orientations of hair cells across the epithelial plane. The cell-intrinsic patterning of hair bundles is implemented independently by the G protein complex classically known for orienting the mitotic spindle. Although the primary cilium also participates in each of these pathways, its role and the integration of the two systems are poorly understood. We show that Dishevelled-associating protein with a high frequency of leucine residues (Daple) interacts with PCP and cell-intrinsic signals. Regulated by the cell-intrinsic pathway, Daple is required to maintain the polarized distribution of the core PCP protein Dishevelled and to position the primary cilium at the abneural edge of the apical surface. Our results suggest that the primary cilium or an associated structure influences the domain of cell-intrinsic signals that shape the hair bundle. Daple is therefore essential to orient and pattern sensory hair bundles.


auditory system; cochlea; hair cell; planar cell polarity; primary cilium

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