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The RFX transcription factor gene, daf-19, has dual funcitons in ciliated and non-ciliated neurons

ABSTRACT: Cilia are required for many sensory and motility related functions and are involved in growing number of genetic disorders termed ciliopathies. DAF-19, RFX type transcription factor controls expression of many cilia structure and function related genes. To this end, transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using selectively staged larval stages where cilia mature and maintained, structurally as well as functionally.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE96068 | GEO | 2018/01/31

REPOSITORIES: GEO

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Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.

Project description:Cilia are ubiquitous cell surface projections that modulate various sensory- and motility based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. As new components required for cilium biogenesis and function remain unidentified, we sought to further define and validate the transcriptional targets of the ciliogenic C. elegans RFX transcription factor DAF-19. To this end, transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using selectively staged embryos where ciliogenesis occurs in most ciliated sensory neurons (CSNs). Statistical comparisons between the two populations revealed 881 differentially regulated genes with 1.5-fold change or greater. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional-GFP fusions revealed CSN-specific expression patterns for 9 of 12 candidate genes. We show that two uncharacterized candidate genes, which we term dyf-17 and dyf-18 because their corresponding mutants display dye-filling (Dyf) defects, are important for ciliogenesis. DYF-17 localizes at the base of cilia and interestingly, is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK-7/CCRK-related serine-threonine kinase that is necessary for the proper function of intraflagellar transport (IFT), a process critical for cilium biogenesis. Together, our comparative microarray study identifies targets of the evolutionarily conserved RFX transcription factor, DAF-19, providing a rich dataset from which to uncover—in addition to DYF-17 and DYF-18—cellular components important for cilium formation and function. 4 daf-19,daf12; 4 daf-12; 4 WT

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An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Nonciliated Neurons.

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