The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT. We demonstrate that while DAF-16/FOXO is dispensable, the age-dependent suppression of cilia phenotypes in IFT mutants requires cell-autonomous functions of the HSF1 heat shock factor and the Hsp90 chaperone. Our results describe an unexpected role of early aging and protein quality control mechanisms in suppressing ciliary phenotypes of IFT mutants, and suggest possible strategies for targeting subsets of ciliopathies.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131903PMC
http://dx.doi.org/10.1371/journal.pgen.1006325DOI Listing

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Article Synopsis
  • - Mutations in cilia genes are linked to ciliopathies, affecting cell functions such as development and survival, particularly in zebrafish lateral line hair cells.
  • - Disruption of cilia due to mutations in IFT genes (ift88 and dync2h1) led to increased hair cell apoptosis and decreased mitochondrial function, suggesting a link between mitochondrial dysfunction and cell death.
  • - While these mutations resulted in reduced hair cell regeneration and survival, they did not significantly alter the number of support cells or their proliferation during hair cell development.
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Intraflagellar transport (IFT) involves the coordinated transport of molecular motors and other proteins and is required for ciliogenesis and ciliary maintenance. The IFT protein OSM-5 /IFT88 is expressed in a majority of the ciliated neurons in the animal, and mutants exhibit structurally defective cilia. The promoter is commonly used to express genetic constructs in the ciliated neurons.

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Cilia play a key role in the regulation of signaling pathways required for embryonic development, including the proper formation of the neural tube, the precursor to the brain and spinal cord. Forward genetic screens were used to generate mouse lines that display neural tube defects (NTD) and secondary phenotypes useful in interrogating function. We describe here the L3P mutant line that displays phenotypes of disrupted Sonic hedgehog signaling and affects the initiation of cilia formation.

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