Crosstalk of MAP3K1 and EGFR signaling mediates gene-environment interactions that block developmental tissue closure.

ABSTRACT: Aberrant regulation of signal transduction pathways can adversely derail biological processes for tissue development. One such process is the embryonic eyelid closure that is dependent on the mitogen-activated protein kinase kinase kinase 1 (MAP3K1). Map3k1 KO in mice results in defective eyelid closure and an autosomal recessive eye-open at birth phenotype. We have shown that in utero exposure to dioxin, a persistent environmental toxicant, induces the same eye defect in Map3k1^+/- heterozygous but not WT pups. Here, we explore the mechanisms of the Map3k1 (gene) and dioxin (environment) interactions (GxE) underlying defective eyelid closure. We show that, acting through the aryl hydrocarbon receptor, dioxin activates epidermal growth factor receptor signaling, which in turn dep

SUBMITTER: Wang J 

PROVIDER: S-EPMC11294703 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature