Monitoring Editor: Marcos Gonzalez-Gaitan Neurons form elaborate subcellular structures such as dendrites, axons, cilia, and synapses to receive signals from their environment and transmit them to the respective target cells. In the worm C. elegans, lack of the RFX transcription factor DAF-19 leads to the complete absence of cilia normally found on 60 sensory neurons. We now describe and functionally characterize three different isoforms of DAF-19. The short isoform DAF-19C is specifically expressed in ciliated sensory neurons and sufficient to rescue all cilia-related phenotypes of
daf-19 mutants. In contrast, the long isoforms DAF-19A/B function in basically all nonciliated neurons. We discovered behavioral and cellular phenotypes in
daf-19 mutants that depend on the isoforms
daf-19a/b. These novel synaptic maintenance phenotypes are reminiscent of synaptic decline seen in many human neurodegenerative disorders. C. elegans
daf-19 mutant worms can thus serve as a molecular model for the mechanisms of functional neuronal decline.