Tfap2e/AP-2ε has both activating and repressive roles in controlling genetic programs of vomeronasal sensory neurons that underly sociosexual behavior in mice

Neuronal identity dictates the position in an epithelium, and the ability to detect, process, and transmit specific signals to specified targets. Transcription factors (TFs) determine cellular identity via direct modulation of genetic transcription and recruiting chromatin modifiers. However, our understanding of the mechanisms that define neuronal identity and their magnitude remains a critical barrier to elucidate the etiology of congenital and neurodegenerative disorders. The rodent vomeronasal organ provides a unique system to examine in detail the molecular mechanisms underlying the differentiation and maturation of chemosensory neurons. Here we demonstrated that the identity of postmitotic/maturing VSNs and vomeronasal dependent behaviors can be reprogrammed through the rescue of AP-2ε expression in the AP-2εNull mice and by inducing ectopic AP-2ε expression in mature apical VSNs. We suggest that the transcription factor AP-2ε can reprogram VSNs bypassing cellular plasticity restrictions, and that it directly controls the expression of batteries of vomeronasal genes. CUT&RUN for TFAP2E in mouse P10 VNO tissue