Transcriptional profiling of C. elegans DAF-19 uncovers a ciliary base-associated protein and a CDK/CCRK/LF2p-related kinase required for intraflagellar transport
| Autor: | Erik M. Jorgensen, Filip Crona, Michel R. Leroux, Brian P. Piasecki, Jan Burghoorn, Kim Schuske, Maria Trieb, Mathieu W. Bakhoum, Prasad Phirke, Swetha Mohan, Peter Swoboda, Evgeni Efimenko |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Sensory Receptor Cells
Transcription Genetic Green Fluorescent Proteins Protein Serine-Threonine Kinases Ciliopathies Article Animals Genetically Modified 03 medical and health sciences Cyclin-dependent kinase Intraflagellar transport Ciliogenesis Animals Cilia Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology 030304 developmental biology 0303 health sciences biology Gene Expression Profiling Cilium 030302 biochemistry & molecular biology Biological Transport Cell Biology biology.organism_classification Cyclin-Dependent Kinases Cell biology Gene expression profiling Mutation biology.protein Ciliary base Transcription Factors Developmental Biology |
| Zdroj: | Developmental Biology. 357:235-247 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2011.06.028 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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