Summary Analysis of xbx genes in C . elegans

Sensory behavior in higher animals depends on the correct recognition and processing of signals from the environment or from within the organism, and then on the appropriate reaction to those signals. The first step in this chain of events, signal recognition, is mediated by specialized cells of the nervous system, the sensory neurons. They create functional compartments for the localization and exposure of the signal reception and transduction machineries. There is considerable diversity in these compartments. Prominent examples are ciliated endings at the tip of dendrites of sensory neurons. Specialized mammalian sensory cilia include those in the photoreceptor cells in the eye, in the hair cells in the ear, and in olfactory neurons in the nose. The universal architecture of cilia and their close relatives, flagella, consists of a microtubular axonemal core enclosed by a membrane, exposed on the cell surface. A convergence of results from several systems has led to detailed structural descriptions of cilia and flagella (Perkins et al., 1986; Dutcher, 1995; Rosenbaum and Witman, 2002). In the nematode C. elegans 60 of the 302 neurons of the hermaphrodite are ciliated sensory neurons (CSN) (Ward et al., 1975; White et al., 1986), forming many structurally distinct types of sensory cilia. Whereas many ciliary mutants are available in C. elegans, there is only one known gene mutation that completely eliminates all classes of sensory cilia and all functional components of cilium structure. This gene is daf-19, and it encodes the sole C. elegans member of the RFX-type transcription factors (Swoboda et al., 2000), found widely in the eukaryotic kingdom. All members of the RFX transcription factor family are characterized by the presence of a conserved DNA binding domain (DBD). The RFX-DBD binds to special motifs (X-boxes) in promoters of its target genes. Genes containing the X-box promoter motif are called xbx genes. Apart from C. elegans DAF-19, the RFX family currently contains nine characterized members: five in mice and humans (RFX1-5) (Emery et al., 1996a), two in Drosophila melanogaster (dRFX1-2) (Dubruille et al., 2002; Otsuki et al., 2004), and one member each from Schizosaccharomyces pombe (Wu and McLeod, 1995) and Saccharomyces cerevisiae (Huang et al., 1998). The data obtained so far suggest diverse biological roles of RFX proteins. In yeasts they regulate some aspects of the cell cycle (Wu and McLeod, 1995; Huang et al., 1998). In humans RFX factors are involved in the transcriptional regulation of major histocompatibility complex class II genes (RFX5) (Reith and Mach, 2001) and in the Cilia and flagella are widespread eukaryotic subcellular components that are conserved from green algae to mammals. In different organisms they function in cell motility, movement of extracellular fluids and sensory reception. While the function and structural description of cilia and flagella are well established, there are many questions that remain unanswered. In particular, very little is known about the developmental mechanisms by which cilia are generated and shaped and how their components are assembled into functional machineries. To find genes involved in cilia development we used as a search tool a promoter motif, the X-box, which participates in the regulation of certain ciliary genes in the nematode Caenorhabditis elegans. By using a genome search approach for X-box promoter motif-containing genes (xbx genes) we identified a list of about 750 xbx genes (candidates). This list comprises some already known ciliary genes as well as new genes, many of which we hypothesize to be important for cilium structure and function. We derived a C. elegans X-box consensus sequence by in vivo expression analysis. We found that xbx gene expression patterns were dependent on particular Xbox nucleotide compositions and the distance from the respective gene start. We propose a model where DAF-19, the RFX-type transcription factor binding to the X-box, is responsible for the development of a ciliary module in C. elegans, which includes genes for cilium structure, transport machinery, receptors and other factors.