title: Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport.
abstract: Cilia are ubiquitous cell surface projections that mediate various sensory- and motility-based processes and are implicated in a growing number of multi-organ genetic disorders termed ciliopathies. To identify new components required for cilium biogenesis and function, we sought to further define and validate the transcriptional targets of DAF-19, the ciliogenic C. elegans RFX transcription factor. Transcriptional profiling of daf-19 mutants (which do not form cilia) and wild-type animals was performed using embryos staged to when the cell types developing cilia in the worm, the ciliated sensory neurons (CSNs), still differentiate. Comparisons between the two populations revealed 881 differentially regulated genes with greater than a 1.5-fold increase or decrease in expression. A subset of these was confirmed by quantitative RT-PCR. Transgenic worms expressing transcriptional GFP fusions revealed CSN-specific expression patterns for 11 of 14 candidate genes. We show that two uncharacterized candidate genes, termed 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 is specifically required for building the distal segment of sensory cilia. DYF-18 is an evolutionarily conserved CDK7/CCRK/LF2p-related serine/threonine kinase that is necessary for the proper function of intraflagellar transport, a process critical for cilium biogenesis. Together, our 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.
authors: Karolinska Institute, Center for Biosciences at NOVUM, Department of Biosciences and Nutrition, Huddinge, Sweden.
authors: Prasad
authors: P
authors: Phirke
authors: Evgeni
authors: E
authors: Efimenko
authors: Swetha
authors: S
authors: Mohan
authors: Jan
authors: J
authors: Burghoorn
authors: Filip
authors: F
authors: Crona
authors: Mathieu W
authors: MW
authors: Bakhoum
authors: Maria
authors: M
authors: Trieb
authors: Kim
authors: K
authors: Schuske
authors: Erik M
authors: EM
authors: Jorgensen
authors: Brian P
authors: BP
authors: Piasecki
authors: Michel R
authors: MR
authors: Leroux
authors: Peter
authors: P
authors: Swoboda
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002923:Cilia / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; C410596:DAF-19 protein, C elegans; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; C562079:DYF-18 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D018844:Cyclin-Dependent Kinases