Interlocked transcription factor feedback loops maintain and restore adult touch sensation

The sense of touch relies on the continuous function of specialized mechanosensory circuits, but the underlying molecular mechanisms remain poorly understood. Here, we report that the conserved transcription factors (TFs) CFI-1 (ARID3) and EGL-5 (HOXA7) jointly maintain in adult Caenorhabditis elegans the molecular identity of two key interneuron types, securing information processing within a mechanosensory circuit. Toggling between normal and low levels of CFI-1 or EGL-5 in adults generates digital-like (ON/OFF) effects both on touch-evoked escape response and interneuron identity. Strikingly, reintroduction of CFI-1 following its prolonged depletion restores escape response defects. Mechanistically, we identify two TF network motifs, a double-positive CFI-1/EGL-5 feedback loop and positive CFI-1 autoregulation, which together "lock-in" the interneuron identity programs. Altogether, this work uncovers a molecular mechanism for maintenance of adult neuron identity and circuit function, offering crucial insights into the restorability of neuronal and behavioral defects caused by mutations or variation in TF-encoding genes.