The fork head transcription factor FKTF-1b from Strongyloides stercoralis restores DAF-16 developmental function to mutant Caenorhabditis elegans

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 datf-16 alpha 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 thecontinuous reproductive cycle, whereas under the same conditions 100% of daf-2 single mutants formed clatters. 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-16 alpha::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. (c) 2005 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.