Evidence item

Here we created a multimodal facial atlas across embryonic weeks 6–11, providing single-cell transcriptomics, chromatin accessibility and spatial transcriptomics, all at single-cell resolution. We characterized 56 cell states, mapping mesenchymal subtypes and their gene–enhancer cis-regulatory landscapes in space and time. Gene expression associations with facial traits were strongest in early mesenchymal progenitor cells, gradually becoming more region restricted. Enhancers of key pathology-related genes were found to be likely vehicles for generating facial variation in modern human populations. One such enhancer, linked to PAX1 expression, appears to be important for normal skeletal development in mice. Finally, facial effects inferred from the genome-wide association study, cell signaling interaction analysis and validation in mice revealed that peripheral nerves fine-tune maxilla shape during embryonic development.