POU4 transcription factors play essential roles in sensory neuron development, however, little is known about their roles in a regenerative context. Here we analyzed the activity of pou4-2 in the planarian Schmidtea mediterranea. Expression analysis revealed that pou4-2 is expressed in ciliated mechanosensory neurons. Inhibition of pou4-2 leads to abnormal sensory neuron regeneration that causes planarians to display rheo- and vibration sensing defects. Additionally, we showed that pou4-2 is downstream of soxB1-2, a transcription factor that is also expressed in mechanosensory neurons. Pou4-2 regulates many downstream targets of soxB1-2. Furthermore, through candidate gene screening, we identified nkx, scratch, foxj1-1, and delta-3 to be involved in the differentiation and regeneration of mid-dorsal ciliated epidermis and/or ciliated mechanosensory neurons. Using RNAi experiments, we established a gene regulatory network to explain how all those genes could potentially interact with one another.
