Abstract
In animals, RFX transcription factors govern ciliogenesis by binding to an X-box motif in the promoters of ciliogenic genes. In Caenorhabditis elegans, the sole RFX transcription factor (TF) daf-19 null mutant lacks all sensory cilia, fails to express many ciliogenic genes, and is defective in many sensory behaviors, including male mating. The daf-19c isoform is expressed in all ciliated sensory neurons and is necessary and sufficient for activating X-box containing ciliogenesis genes. Here, we describe the daf-19(n4132) mutant that is defective in expression of the sensory polycystic kidney disease (PKD) gene battery and male mating behavior, without affecting expression of ciliogenic genes or ciliogenesis. daf-19(n4132) disrupts expression of a new isoform, daf-19m (for function in male mating). daf-19m is expressed in male-specific PKD and core IL2 neurons via internal promoters and remote enhancer elements located in introns of the daf-19 genomic locus. daf-19m genetically programs the sensory functions of a subset of ciliated neurons, independent of daf-19c. In the male-specific HOB neuron, DAF-19(M) acts downstream of the zinc finger TF EGL-46, indicating that a TF cascade controls the PKD gene battery in this cell-type specific context. We conclude that the RFX TF DAF-19 regulates ciliogenesis via X-box containing ciliogenic genes and controls ciliary specialization by regulating non-X-box containing sensory genes. This study reveals a more extensive role for RFX TFs in generating fully functional cilia.
Highlights
CILIA and flagella are highly conserved structures that fulfill important functions in motility, development, and sensation (Marshall and Nonaka 2006; Scholey and Anderson 2006)
We describe the daf-19(n4132) mutant that is defective in expression of the sensory polycystic kidney disease (PKD) gene battery and male mating behavior, without affecting expression of ciliogenic genes or ciliogenesis. daf-19(n4132) disrupts expression of a new isoform, daf-19m. daf-19m is expressed in malespecific PKD and core IL2 neurons via internal promoters and remote enhancer elements located in introns of the daf-19 genomic locus. daf-19m genetically programs the sensory functions of a subset of ciliated neurons, independent of daf-19c
Studies on Caenorhabditis elegans daf-19, the sole Regulatory factor X (RFX) transcription factor (TF) in the worm, provided important insight into the role of RFX TFs in regulating ciliogenesis and ciliogenic gene batteries (Swoboda et al 2000; Blacque et al 2005; Chen et al 2006; Senti and Swoboda 2008; Senti et al 2009). daf-19 null mutants fail to express many ciliogenic genes, lack all sensory cilia, and are defective in many sensory behaviors (Perkins et al 1986; Collet et al 1998; Swoboda et al 2000; Efimenko et al 2005). daf-19 encodes three isoforms: DAF-19A/B functions in nonciliated neurons to maintain synaptic activity in the adult, while DAF-19C is expressed in all ciliated sensory neurons to regulate ciliogenesis (Senti and Swoboda 2008)
Summary
CILIA and flagella are highly conserved structures that fulfill important functions in motility, development, and sensation (Marshall and Nonaka 2006; Scholey and Anderson 2006). The male has an additional 48 sex-specific ciliated sensory neurons required for mating behaviors (Sulston et al 1980; Liu and Sternberg 1995; Barr and Sternberg 1999). These cilia may exhibit unique morphologies, express distinct repertoires of receptors and signaling molecules, and function in a variety of sensory modalities (Bae and Barr 2008). Consistent with sensory function in RnB and HOB neurons, lov-1, pkd-2, and klp-6 mutant males are response (Rsp) and location of vulva (Lov) defective
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