Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, United States; School of Biological Sciences, University of Auckland, Auckland, New Zealand
Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, United States
Kyle C Chipman
Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, United States
Emily R Mears
School of Biological Sciences, University of Auckland, Auckland, New Zealand
Cricket G Wood
Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, United States
Coco Emma Alma Al-Alami
School of Biological Sciences, University of Auckland, Auckland, New Zealand
Melissa R Alcorn
Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, United States
Thomas L Turner
Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, Santa Barbara, United States
Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, United States
Russell G Snell
School of Biological Sciences, University of Auckland, Auckland, New Zealand
Department of MCD Biology, University of California, Santa Barbara, Santa Barbara, United States; School of Biological Sciences, University of Auckland, Auckland, New Zealand; Department of Ecology, Evolution, and Marine Biology, University of California, Santa Barbara, Santa Barbara, United States; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, United States
Innovations in metazoan development arise from evolutionary modification of gene regulatory networks (GRNs). We report widespread cryptic variation in the requirement for two key regulatory inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm GRN. While some natural isolates show a nearly absolute requirement for these two regulators, in others, most embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. We observe a reciprocal trend, in which genomic variants, or knockdown of endoderm regulatory genes, that result in a high SKN-1 requirement often show low MOM-2/Wnt requirement and vice-versa, suggesting that cryptic variation in the endoderm GRN may be tuned by opposing requirements for these two key regulatory inputs. These findings reveal that while the downstream components in the endoderm GRN are common across metazoan phylogeny, initiating regulatory inputs are remarkably plastic even within a single species.
