title: A conserved endocrine mechanism controls the formation of dauer and infective larvae in nematodes.
abstract: Under harsh environmental conditions, Caenorhabditis elegans larvae undergo arrest and form dauer larvae that can attach to other animals to facilitate dispersal. It has been argued that this phenomenon, called phoresy, represents an intermediate step toward parasitism. Indeed, parasitic nematodes invade their hosts as infective larvae, a stage that shows striking morphological similarities to dauer larvae. Although the molecular regulation of dauer entry in C. elegans involves insulin and TGF-beta signaling, studies of TGF-beta orthologs in parasitic nematodes didn't provide evidence for a common origin of dauer and infective larvae. To identify conserved regulators between Caenorhabditis and parasitic nematodes, we used an evolutionary approach involving Pristionchus pacificus as an intermediate. We show by mutational and pharmacological analysis that Pristionchus and Caenorhabditis share the dafachronic acid-DAF-12 system as the core endocrine module for dauer formation. One dafachronic acid, Delta7-DA, has a conserved role in the mammalian parasite Strongyloides papillosus by controlling entry into the infective stage. Application of Delta7-DA blocks formation of infective larvae and results in free-living animals. Conservation of this small molecule ligand represents a fundamental link between dauer and infective larvae and might provide a general strategy for nematode parasitism.
authors.affiliation: Department for Evolutionary Biology, Max-Planck Institute for Developmental Biology, Spemannstrasse 37, D-72076 Tübingen, Germany.
authors.forename: Akira
authors.initials: A
authors.lastname: Ogawa
authors.forename: Adrian
authors.initials: A
authors.lastname: Streit
authors.forename: Adam
authors.initials: A
authors.lastname: Antebi
authors.forename: Ralf J
authors.initials: RJ
authors.lastname: Sommer
mesh_terms: D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002782:Cholestenes / Q000378:metabolism / Q000494:pharmacology*; D017124:Conserved Sequence / Q000235:genetics; D007814:Larva / Q000187:drug effects / Q000502:physiology; D008018:Life Cycle Stages / Q000187:drug effects*; D010641:Phenotype; D010802:Phylogeny; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity
chemical_list: D029742:Caenorhabditis elegans Proteins; D002782:Cholestenes; C410905:DAF-12 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; C533798:delta7-dafachronic acid