PT  - JOURNAL ARTICLE
AU  - Yamila N. Torres Cleuren
AU  - Chee Kiang Ewe
AU  - Kyle C. Chipman
AU  - Emily Mears
AU  - Cricket G. Wood
AU  - Coco Al-Alami
AU  - Melissa R. Alcorn
AU  - Thomas L. Turner
AU  - Pradeep M. Joshi
AU  - Russell G. Snell
AU  - Joel H. Rothman
TI  - Reciprocal requirement of Wnt signaling and SKN-1 underlies cryptic intraspecies variation in an ancient embryonic gene regulatory network
AID  - 10.1101/628495
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 628495
4099  - http://biorxiv.org/content/early/2019/05/05/628495.short
4100  - http://biorxiv.org/content/early/2019/05/05/628495.full
AB  - Innovations in metazoan development arise from evolutionary modifications of gene regulatory networks (GRNs). We report large cryptic variation in the requirement for two key inputs, SKN-1/Nrf2 and MOM-2/Wnt, into the C. elegans endoderm-determining GRN. Some natural variants show a nearly absolute requirement for SKN-1 and MOM-2, while in others, most of the embryos differentiate endoderm in their absence. GWAS and analysis of recombinant inbred lines reveal multiple genetic regions underlying this broad phenotypic variation. A striking reciprocal relationship is seen in which genomic variants, or debilitation of genes involved in endoderm formation, that result in high SKN-1 requirement show low MOM-2/Wnt requirement and vice-versa. Thus, 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 metazoans, initiating regulatory inputs are remarkable plastic even within a single species.