Our results show that the principle role of HPO-30 is to stabilize pioneer 2° branches ( Figure 7) and, thus, that additional unknown factors may drive fasciculation with motor neuron commissures ( Smith et al., 2010). Because claudins serve as key constituents of junctions between adjacent cells ( Simske and Hardin, 2011, Steed

et al., 2010 and Tsukita and Furuse, 2000), it seems likely that HPO-30 functions in this case to link growing 2° dendrites with the nematode epidermis. We note that an additional membrane component, the LRR protein DMA-1, displays a mutant PVD branching phenotype strongly resembling that of Hpo-30 and therefore could also function in this pathway ( Liu and Shen, 2012). The intimate association of topical sensory arbors with the skin ( Delmas et al., 2011, Han et al., 2012 and Kim NLG919 order et al., AG14699 2012) and the broad conservation of junctional proteins

across species ( Labouesse, 2006 and Steed et al., 2010) point to the likelihood that homologs of HPO-30/Claudin and similar components could be widely utilized to pattern sensory neuron morphogenesis. ahr-1 encodes a member of the bHLH-PAS family of transcription factors and is the nematode homolog of the aryl hydrocarbon receptor (AHR) protein. In mammals, AHR is activated by the xenobiotic compound dioxin to trigger a wide range of pathological effects ( Wilson and Safe, 1998). Invertebrate AHR proteins are not activated by dioxin, which suggests that this toxin-binding function represents an evolutionary adaptation unique to vertebrates ( Hahn, 2002 and Powell-Coffman et al., 1998). An ancestral role for AHR is suggested by AHR mutants in C. elegans and Drosophila that display distinct developmental defects

in which a given cell type or tissue adopts an alternative fate ( Huang et al., 2004 and Struhl, Mephenoxalone 1982). For example, stochastic expression of the Drosophila AHR homolog, Spineless, promotes the adoption of one specific photoreceptor sensory neuron identity at the expense of another ( Wernet et al., 2006). Our results parallel these findings with the demonstration that AHR-1 function is required in C. elegans to distinguish between alternative types of mechanosensory neurons; in ahr-1 mutants, the unbranched light touch neuron, AVM, is transformed into a functional homolog of the highly branched PVD nociceptor. This role for ahr-1 in C. elegans is particularly notable because the AHR-1 homolog, Spineless, also regulates branching complexity in Drosophila. In spineless (Ss) mutants, Class I and II sensory neurons, which normally display simple branching patterns, adopt more complex dendritic arbors ( Kim et al., 2006). This phenotype resembles our finding in C. elegans that the simple morphology of the AVM neuron is transformed into the highly branched architecture of the PVD nociceptor in ahr-1 mutants.