Uncovering hidden Wnt/beta-catenin enhancer in Caenorhabditis elegans

Background: Wnt/ß-catenin pathway is well conserved along metazoans and plays an essential role in important cellular functions such as specialization, migration, adhesion and development. Mutant analyses in C. elegans strain Bristol N2 have been widely studied. However mutations in a single genetic background do not reveal genome-wide allelic effects in natural populations and they are of limited value in the approach of complex human disease pathways, for which C. elegans is an important model species. Observations: Mutations in natural variants may revealed hidden polymorphic regulators, thus we investigated the phenotypic effects of bar-1(ga80) in a population of different C. elegans genotypes. Each genotype carries the bar-1 mutation in a genetic mosaic background resulting from the recombination of two of the most divergent C. elegans strains genotypes: Bristol N2 and Hawaii CB4856. We quantified genome-wide gene expression and measured the vulval development index (determined by the number of vulval precursor cells that undergo vulval development cell fate) and gonad migration across all genotypes. Quantitative genetics analysis identified loci on chromosome I and II which are associated to vulval development and gonad migration phenotypes. The two loci spanned regions of 300 Kbp on chromosome I harbouring 100 genes and 55 Kbp containing 15 genes on chromosome II. Experiments will be presented to reveal the candidate gene that plays the causal modifier role. Continue Conclusions: By applying forward genetics in different genotypes we have revealed hidden genetic modifiers affecting Wnt signalling pathway. We show that natural genetic variation provides a powerful means to study the cryptic variation harbouring new players in Wnt/ ß-catenin signalling.