Pcdh20 is a POU2F3 target gene required for proper tuft cell microvillus formation

Tuft cells are solitary chemosensory cells known for their distinct tall, blunt microvilli, thought to be analogous to mechanosensory hair cell stereocilia. Identification of commonalities between tuft and hair cells could identify a role for tuft cells in mechanotransduction. Transcription factor POU2F3 is the master regulator of tuft cell formation, however how POU2F3 drives formation of this unique cell and the functional role of the microvillar apparatus is unknown. POU2F3 ChIP-seq was performed on isolated tuft cells and compared to the cochlear hair cell transcriptome. Structural genes common to both tuft and hair cells, including protocadherin 20 (PCDH20), were identified. Immunogold labeling and imaging localized PCDH20 to extensive intermicrovillar linkages in tuft cells. Knockdown of PCDH20 in mice resulted in impaired microvilli formation and a disruption in structure. Altogether, PCDH20 is a POU2F3 target gene in tuft cells critical to maintain the rigid microvillar apparatus, which may function in mechanotransduction.