Cryptic quantitative evolution of the vulva intercellular signaling network in Caenorhabditis

Background: The Caenorhabditis vulva is formed from a row of Pn.p precursor cells, which adopt a spatial cell-fate pattern-3 degrees 3 degrees 2 degrees 1 degrees 2 degrees 3 degrees-centered on the gonadal anchor cell. This pattern is robustly specified by an intercellular signaling network including EGF/Ras induction from the anchor cell and Delta/Notch signaling between the precursor cells. It is unknown how the roles and quantitative contributions of these signaling pathways have evolved in closely related Caenorhabditis species. Results: Cryptic evolution in the network is uncovered by quantification of cell-fate-pattern frequencies obtained after displacement of the system out of its normal range, either by anchor-cell ablations or through LIN-3/EGF overexpression. Silent evolution in the Caenorhabditis genus covers a large neutral space of cell-fate patterns. Direct induction of the 1 degrees fate as in C. elegans appeared within the genus. C. briggsae displays a graded induction of 1 degrees and 2 degrees fates, with 1 degrees fate induction requiring a longer time than in C. elegans, and a reduced lateral inhibition of adjacent 1 degrees fates. C. remanei displays a strong lateral induction of 2 degrees fates relative to vulval-fate activation in the central cell. This evolution in cell-fate pattern space can be experimentally reconstituted by mild variations of Ras, Wnt, and Notch pathway activities in C. elegans and C. briggsae. Conclusions: Quantitative evolution in the roles of graded induction by LIN-3/EGF and Notch signaling is demonstrated for the Caenorhabditis vulva signaling network. This evolutionary system biology approach provides a quantitative view of the variational properties of this biological system.