(A) Under normal conditions, signaling from the posterior P2 cell (Wnt, MAPK and Src) results in asymmetric cortical localization of Wnt signaling pathway components in EMS leading to POP-1 asymmetry in the descendants of EMS, with high levels of nuclear POP-1 in anterior MS and low levels of nuclear POP-1 in the posterior, E, daughter cell. In the anterior MS cell, high nuclear POP-1 represses the END genes, allowing SKN-1 to activate MS fate. In the posterior E cell, which remains in contact with P2, POP-1 is converted to an activator and, along with SKN-1, activates the END genes, resulting in endoderm fate. Loss of skn-1, either by RNAi or in loss-of-function mutants, causes 100% of the embryos to arrest; in 70% of the arrested embryos, EMS gives rise to two C-like cells, while in the remaining 30% only MS is converted to a C fate; the posterior daughter retains its E fate. Loss of mom-2 leads to 100% embryonic arrest with a partially penetrant E→MS cell fate transformation, resulting in two MS-like daughter cells in ~72% of the embryos. (B) Regulatory logic of SKN-1 and POP-1 in E specification in C. elegans, C. briggsae and a hypothetical intermediate state. POP-1* denotes the activated state. (C-H) Gut visualization in embryos affected by skn-1 RNAi. (C-E) arrested embryos without endoderm, (F-H) arrested embryos with endoderm. (C, F) DIC images of arrested embryos ~ 12 hr after egg laying. (D, G) the same embryos expressing the gut-specific elt-2::GFP reporter, and (E,H) birefringent gut granules under polarized light. All embryos showing gut birefringence also show elt-2::GFP expression. (I, J) Fields of arrested skn-1(RNAi) embryos in wild isolate strains JU1491 (I) and JU440 (J), which reflect the extremes in the spectrum of requirement of SKN-1 in gut development at 0.9% and 60%, respectively.