Cis-regulatory evolution shapes facial diversity in birds and mammals
Birds and mammals exhibit extraordinary facial diversity, reflecting adaptations to distinct ecological niches and feeding strategies. While core face-building developmental programs are conserved and orchestrated by interactions between ectodermal organizers and underlying mesenchyme, mechanisms driving facial shape variation remain poorly understood. Here, we integrate single-cell transcriptomic and chromatin accessibility profiling of mouse and chicken developing face to construct a comparative regulatory map. Although both ectodermal and mesenchymal populations display distinct regulatory features in each species, the mesenchyme exhibits markedly greater divergence, pointing to its central role in shaping facial morphology. We further reveal unexpected molecular complexity in main face-shaping organizer, including a mouse-specific Shh/Wnt5a expression domain. At key morphogen loci (Bmp4, Fgf8, Wnt5a), conserved and lineage-specific enhancers exhibit spatially restricted activity patterns that mirror divergent signaling domains. These findings demonstrate how cis-regulatory evolution modulates conserved developmental programs to generate morphological novelty, providing a valuable resource for studying vertebrate facial evolution.
Microscopy images:
Interactive single-cell RNA-seq data:
Interactive single-cell ATAC-seq data: