Progressive correction of auditory hair cell orientation in the absence of core planar cell polarity and GPR156 signaling

Planar cell polarity (PCP) proteins, including Van Gogh-like and Frizzled, orient sensory hair cells in the inner ear. Because most PCP mouse models die at birth, orientation defects have been studied mainly at fetal stages. Using viable conditional mutants lacking both Vangl1/Vangl2 or Frizzled3/Frizzled6, we show that misoriented auditory hair cells undergo extensive postnatal reorientation, largely correcting defects over time. These findings extend previous observations in Vangl2 single conditional mutants and demonstrate that correction does not require redundant core PCP partners. GPR156, a receptor that reverses how PCP signaling is interpreted in some hair cell types, is also essential for orientation but Gpr156 mutants fail to correct defects. We therefore tested its role in core PCP mutant recovery. GPR156 binds and depends on VANGL proteins, yet inhibiting GPR156 signaling facilitates rather than prevents correction in Vangl and Frizzled mutants. Thus, GPR156 collaborates with core PCP components to establish hair cell orientation but is dispensable-and even inhibitory-for postnatal realignment. These findings reveal extensive plasticity in hair cell orientation and identify GPR156 as a context-dependent partner of core PCP proteins.