RT Journal Article SR Electronic T1 Extensive intraspecies cryptic variation in an ancient embryonic gene regulatory network JF bioRxiv FD Cold Spring Harbor Laboratory SP 628495 DO 10.1101/628495 A1 Yamila N. Torres Cleuren A1 Chee Kiang Ewe A1 Kyle C. Chipman A1 Emily Mears A1 Cricket G. Wood A1 Coco A.E. Al-Alami A1 Melissa R. Alcorn A1 Thomas L. Turner A1 Pradeep M. Joshi A1 Russell G. Snell A1 Joel H. Rothman YR 2019 UL http://biorxiv.org/content/early/2019/07/31/628495.abstract AB 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 variants 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.