Kavli Affiliate: A. James Hudspeth
| Authors: Swarna Jeewajee, Francesco Gianoli, Maria Jussila, Brian Ciruna, Aaron Steiner, Adrian Jacobo and Albert James Hudspeth
| Summary:
The conserved core planar cell polarity (PCP) pathway orients cells and subcellular structures within an epithelium through asymmetric protein localization and intercellular communication(1–4). In vestibular organs and lateral-line neuromasts, mechanosensory hair cells are interspersed among support cells and form opposing hair-bundle orientations along a shared axis, enabling bidirectional sensitivity to head motion and water flow, respectively(5–9). In zebrafish neuromasts, Notch-mediated lateral inhibition gives rise to two hair-cell populations, distinguished by differential Emx2 expression, that orient their cell-intrinsic polarity machinery differently relative to a PCP-dependent tissue-wide axis(10–14). However, it remains unclear how PCP proteins are organized across hair cells and support cells to achieve both opposing hair-bundle orientations and tissue-wide alignment, and whether PCP signaling remains required after hair-bundle polarity is established. Combining quantitative spatial mapping of the core PCP protein Vangl2 with cell-type-specific and temporally controlled protein degradation, we show that hair cells and support cells make distinct yet coordinated contributions to the polarized Vangl2 organization within neuromasts and to bidirectional hair-bundle polarity. Support-cell Vangl2 facilitates tissue-wide alignment of hair bundles along the anteroposterior axis, whereas hair-cell Vangl2 is required to generate opposing hair-bundle orientations along this axis. Vangl2 degradation after hair bundles have formed disrupts their tissue-wide alignment, showing that planar polarity is actively maintained rather than fixed after establishment. Together, these findings reveal how Vangl2-dependent PCP signaling is distributed across distinct cell types within a heterogeneous epithelium to generate opposing polarity outcomes and remains necessary to preserve tissue-level planar organization.