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

Abstract

Primary cilia are microtubule-based organelles that mediate cellular responses to environmental cues. Although cilia disassemble and reassemble upon cell cycle entry and exit, respectively, in dividing cells, it remains unclear 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 regrows following conditional truncation and restores neuronal functions. 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 required for regeneration, in part via transcriptional upregulation of a subset of ciliary intraflagellar transport (IFT) genes. We further 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 developmental ciliogenesis. We show that cebp-1 expression is induced during cilia truncation and regrowth and that this induction is also DAF-19-dependent. 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.