Neuron-intrinsic and glial pathways regulate sensory cilia regeneration in adult C. elegans

Primary cilia are microtubule-based organelles essential for transducing environmental signals. While cilia reassemble upon cell cycle exit in dividing cells, it remains largely unknown whether postmitotic cells such as neurons can regenerate these structures in vivo following injury to restore function, and whether this process recapitulates developmental ciliogenesis. Here we show that a subset of sensory neuron cilia in adult C. elegans can regrow and restore neuronal functions following conditional truncation. This regeneration is regulated by both cell-intrinsic and extrinsic mechanisms that are in part distinct from those employed during embryonic ciliogenesis. We find that the conserved ciliogenic DAF-19 RFX transcription factor is dispensable for cilia maintenance in the adult but is essential for regrowth, in part via transcriptional upregulation of a subset of ciliary intraflagellar transport (IFT) genes. We also identify the DLK-1 dual leucine-zipper kinase and the CEBP-1 C/EBP transcription factor previously implicated in axon regeneration as necessary for efficient cilia regrowth but not for ciliogenesis. Finally, we show that cilia truncation and regeneration dynamics vary in a neuron type-specific manner and are modulated by signals from surrounding glia. Our results establish that the cilia of mature neurons can regenerate and recover functions in vivo and identify conserved pathways that regulate this process in adult animals.