| First Author | Xiao B | Year | 2026 |
| Journal | iScience | Volume | 29 |
| Issue | 6 | Pages | 115853 |
| PubMed ID | 42109862 | Mgi Jnum | J:389429 |
| Mgi Id | MGI:8344201 | Doi | 10.1016/j.isci.2026.115853 |
| Citation | Xiao B, et al. (2026) MAP3K1 integrates RhoA/ROCK signaling to regulate epithelial morphogenesis. iScience 29(6):115853 |
| abstractText | Biological processes rely on the interplay between genetic and environmental cues, yet the mechanisms underlying gene-gene (GxG) and gene-environment (GxE) interactions remain poorly understood. Using mouse embryonic eyelid closure as an experimentally tractable model, we extend the established S1PR-MAP3K1-JNK signaling axis by identifying a RhoA-ROCK branch as a functionally integrated component of the MAP3K1 network. These pathways converge on paxillin phosphorylation and c-Jun activation, coupling cytoskeletal remodeling with AP-1-dependent transcriptional responses. TurboID-based proximity proteomics identifies Gbeta2 and RhoGEF1/5 as candidate intermediates linking MAP3K1 to S1PR and RhoA. Genetic analyses reveal that Rhoa or Rock1 loss alone is harmless, whereas their combined deficiency or single-gene loss in the context of Map3k1 heterozygosity, S1pr deletion, or dioxin exposure disrupts eyelid closure. These findings define RhoA-ROCK as an integral module within a broader MAP3K1 regulatory network that integrates genetic and environmental inputs to ensure robust morphogenesis. |
