[
1985]
Expression of the vitellogenin genes is restricted to the intestine of adult hermaphrodite C. elegans. In order to identify potential cis-acting elements involved in this developmental regualtion, we have sequenced the regions surrounding the 5' ends of five of the six members of this gene family. In addition, we have sequenced several of the promoters from the homologous genes from the related species C. briggsae. Although the various promoters are largely diverged from one another, we have discovered two potential regulatory sequences within the first 250 bp upstream of each of the genes. The first, TGTCAAT, occurs eight times as a perfect heptamer upstream of the five C. elegans genes, at least once per promoter. Allowing a 1 bp mismatch, the element is found in both orientations a total of 27 times, four to six timer per promoter. It is present preferentially at two locations: just upstream of the TATA box and, in the opposite orientation, at position -180. The second sequence, CTGATAA, is also present as a perfect heptamer in a restricted region of each promoter: near position -135. Remarkably, this sequence is also found upstream of the vitellogenin genes of vertebrates. Both sequences have been conserved in the C. briggsae promoters. We hypothesize that these two sequences are involved in the sex-, tissue-, and stage-specific expression of the vitellogenin genes.
[
Adv Exp Med Biol,
2010]
Nematode neuropeptide systems comprise an exceptionally complex array of approximately 250 peptidic signaling molecules that operate within a structurally simple nervous system of approximately 300 neurons. A relatively complete picture of the neuropeptide complement is available for Caenorhabditis elegans, with 30 flp, 38 ins and 43 nlp genes having been documented; accumulating evidence indicates similar complexity in parasitic nematodes from clades I, III, IV and V. In contrast, the picture for parasitic platyhelminths is less clear, with the limited peptide sequence data available providing concrete evidence for only FMRFamide-like peptide (FLP) and neuropeptide F (NPF) signaling systems, each of which only comprises one or two peptides. With the completion of the Schmidtea meditteranea and Schistosoma mansoni genome projects and expressed sequence tag datasets for other flatworm parasites becoming available, the time is ripe for a detailed reanalysis ofneuropeptide signalingin flatworms. Although the actual neuropeptides provide limited obvious value as targets for chemotherapeutic-based control strategies, they do highlight the signaling systems present in these helminths and provide tools for the discovery of more amenable targets such as neuropeptide receptors or neuropeptide processing enzymes. Also, they offer opportunities to evaluate the potential of their associated signaling pathways as targets through RNA interference (RNAi)-based, target validation strategies. Currently, within both helminth phyla, theflp signaling systems appear to merit further investigation as they are intrinsically linked with motor function, a proven target for successful anti-parasitics; it is clear that some nematode NLPs also play a role in motor function and could have similar appeal. At this time, it is unclear if flatworm NPF and nematode INS peptides operate in pathways that have utility for parasite control. Clearly, RNAi-based validation could be a starting point for scoring potential target pathways within neuropeptide signaling for parasiticide discovery programs. Also, recent successes in the application of in planta-based RNAi control strategies for plant parasitic nematodes reveal a strategy whereby neuropeptide encoding genes could become targets for parasite control. The possibility of developing these approaches for the control of animal and human parasites is intriguing, but will require significant advances in the delivery of RNAi-triggers.