The level of protein in the maternal diet modulates facial appearance via mTORC1 signaling

To elucidate enhancers participating in sculpting human face, we performed CAGE-sequencing of facial mesenchyme of human embryos and cross-referenced identified active enhancers against GWAS datasets for human normal-range facial appearance. Among identified single nucleotide polymorphisms (SNPs) in the active cis-enhancers, several belonged to the components of mTORC1 (Mechanistic Target of Rapamycin Complex 1) pathway. To assess the role of this pathway functionally, genetic and pharmacological manipulations of mTORC1 pathway in mice and zebrafish were performed. They revealed the modulatory role of mTORC1 signaling in fine craniofacial shaping. Overall design: CAGE-sequencing performed on human facial embryonic material (3-12 weeks).