Citation | De Stasio EA, Mueller KP, Bauer RJ, Hurlburt AJ, Bice SA, Scholtz SL, Phirke P, Sugiaman-Trapman D, Stinson LA, Olson HB, Vogel SL, Ek-Vazquez Z, Esemen Y, Korzynski J, Wolfe K, Arbuckle BN, Zhang H, Lombard-Knapp G, Piasecki BP, Swoboda P. An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Non-ciliated Neurons. Genetics, 2018. |
PubMed ID | 29301909 |
Short Description | An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Non-ciliated Neurons. GEO Record: GSE96068 Platform: GPL200 Download gene-centric, log2 transformed data: WBPaper00053550.ce.mr.csv |
# of Conditions | 14 |
Full Description | Regulatory Factor X transcription factors (RFX TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans, the sole RFX gene, daf-19, encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons and whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is down-regulated in the presence of DAF-19, primarily in non-sensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for down-regulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform (tm5562) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. We have thus identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects daf-19 exerts on nervous system function. Experimental Details: WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep1 WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep2 WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep3 WBPaper00053550:L1_daf-19(m86);daf-12(sa204)_rep4 WBPaper00053550:L1_daf-12(sa204)_rep1 WBPaper00053550:L1_daf-12(sa204)_rep2 WBPaper00053550:L1_daf-12(sa204)_rep3 WBPaper00053550:L1_daf-12(sa204)_rep4 WBPaper00053550:2-Day-Adult_daf-19(m86);daf-12(sa204)_rep1 WBPaper00053550:2-Day-Adult_daf-19(m86);daf-12(sa204)_rep2 WBPaper00053550:2-Day-Adult_daf-19(m86);daf-12(sa204)_rep3 WBPaper00053550:2-Day-Adult_daf-12(sa204)_rep1 WBPaper00053550:2-Day-Adult_daf-12(sa204)_rep2 WBPaper00053550:2-Day-Adult_daf-12(sa204)_rep3. |
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