Planar polarized organization of mouse hair cells is established and maintained by STK32A, GPR156 and EMX2.

Document Type

Article

Publication Date

12-1-2025

Keywords

JMG, Animals, Receptors, G-Protein-Coupled, Cell Polarity, Mice, Protein Serine-Threonine Kinases, Hair Cells, Auditory, Homeodomain Proteins, Transcription Factors, Serine-Threonine Kinase 3

JAX Source

J Cell Sci. 2025;138(23).

ISSN

1477-9137

PMID

41208475

DOI

https://doi.org/10.1242/jcs.264340

Grant

R01DC018304 to B.T.

Abstract

Hair cells in the utricle and saccule form two groups with oppositely oriented stereociliary bundles that enable detection of broad ranges of motion. These groups are aligned along a common polarity axis established by core planar cell polarity (PCP) proteins, which individual cells interpret differently to generate opposing bundle orientations. EMX2, GPR156 and STK32A determine how these groups integrate PCP signaling during this process. We tested functional interactions between these factors using genetic epistasis experiments and evaluating hair cells in mice with combined mutations in Gpr156 and Stk32a or Emx2 and Stk32a. We show in the utricle that: (1) GPR156 functions to reverse stereociliary bundles relative to the PCP axis but can be blocked by STK32A; and (2) EMX2 establishes the boundary between the two groups by repressing Stk32a transcription. We further demonstrate that these factors have similar functional relationships in the cochlea, despite the absence of polarity reversal in that tissue. Together, these phenotypes support a mechanism whereby EMX2 regulates Stk32a transcription, thereby allowing GPR156 to reverse the orientation of stereociliary bundles in one group of hair cells.

Share

COinS