McCubbin, R. A.; Auwal, M. A.; Wang, S.; Zepeda, S. A.; Sasik, R.; Zeller, R. W.; Ross, K. G.; Zayas, R. M.

POU4 homologs are involved in the development of sensory cell types across diverse species, including cnidarians, ascidians, and mammals. Whether these developmental regulators are reused during adult tissue maintenance and regeneration remains a fundamental question in regenerative biology. Here, we investigate the role of the Schmidtea mediterranea BRN3/POU4 homolog, Smed-pou4-2 (pou4-2), in the regeneration of mechanosensory neurons. We find that pou4-2 is regulated by the SoxB1 homolog, soxB1-2, and is expressed in a distinct population of ciliated sensory cells that detect water flow. Transcriptomic analysis of pou4-2-deficient planarians reveals enrichment for conserved genes associated with human auditory and vestibular function, suggesting that planarian rheosensory neurons share molecular features with mammalian inner ear hair cells. Expression of these conserved genes is abrogated by RNAi-mediated knockdown of pou4-2. To determine whether these transcriptional changes had functional consequences for mechanosensory neuron identity or behavior, we next assessed the impact of pou4-2 knockdown on sensory function. pou4-2 RNAi results in impaired mechanosensation in both uninjured and regenerating planarians. Together with the loss of terminal differentiation markers in mechanosensory neurons, these findings identify Smed-pou4-2 as a key regulator of mechanosensory neuron identity in planarians and support the idea that conserved sensory specification programs are redeployed during adult tissue regeneration.