title: The fork head transcription factor FKTF-1b from Strongyloides stercoralis restores DAF-16 developmental function to mutant Caenorhabditis elegans.
abstract: The purpose of this study was to determine whether Strongyloides stercoralis FKTF-1, a transcription factor of the FOXO/FKH family and the likely output of insulin/IGF signal transduction in that parasite, has the same or similar developmental regulatory capabilities as DAF-16, its structural ortholog in Caenorhabditis elegans. To this end, both splice variants of the fktf-1 message were expressed under the control of the daf-16alpha promoter in C. elegans carrying loss of function mutations in both daf-2 (the insulin/IGF receptor kinase) and daf-16. Under well-fed culture conditions the majority (91%) of untransformed daf-2; daf-16 double mutants developed via the continuous reproductive cycle, whereas under the same conditions 100% of daf-2 single mutants formed dauers. Transgenic daf-2; daf-16 individuals expressing fktf-1b showed a reversal of the double mutant phenotype with 75% of the population forming dauers under well-fed conditions. This phenotype was even more pronounced than that of daf-2; daf-16 mutants transformed with a homologous rescuing construct, daf-16alpha::daf-16a (56% dauers under well fed conditions), indicating that S. stercoralis fktf-1b can almost fully rescue loss-of-function mutants in C. elegans daf-16. By contrast, daf-2; daf-16 mutants expressing S. stercoralis fktf-1a, encoding the second splice variant of FKTF-1, showed a predominantly continuous pattern of development identical to that of the parental double mutant stock. This indicates that, unlike FKTF-1b, the S. stercoralis transcription factor FKTF-1a cannot trigger the shift to dauer-specific gene expression in C. elegans.
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors.forename: Holman C
authors.initials: HC
authors.lastname: Massey
authors.forename: Mahendra K
authors.initials: MK
authors.lastname: Bhopale
authors.forename: Xinshe
authors.initials: X
authors.lastname: Li
authors.forename: Michelle
authors.initials: M
authors.lastname: Castelletto
authors.forename: James B
authors.initials: JB
authors.lastname: Lok
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018509:DNA, Helminth / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018014:Gene Transfer Techniques; D017238:Genes, Helminth / Q000235:genetics; D015801:Helminth Proteins / Q000235:genetics; D007328:Insulin / Q000235:genetics; D007814:Larva / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D017171:Strongyloides stercoralis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D051858:Forkhead Transcription Factors; D015801:Helminth Proteins; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans