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To the point:
Same genes, different outcomes: Birds and mammals use the same genes to build their face, but deploy them differently in time and space.
Cells and evolutionary change: The undifferentiated facial mesenchyme emerges as an essential cellular source of facial shape variation.
Link to humans: Many regulatory regions active during facial development of mouse and chicken overlap with genomic regions associated with human facial variation.
Shapes of beaks and snouts come in an extraordinary range of forms, reflecting adapta-tions to different lifestyles and environments. Yet beneath this diversity lies a paradox: across birds and mammals, faces are built using deeply conserved developmental pro-grams. So how does evolution generate such striking differences without reinventing the underlying machinery?
A new study led by Dr. Markéta Kaucká at the Max Planck Institute for Evolutionary Biology, in collaboration with Dr. Axel Visel and Dr. Laura Cook from the Lawrence Berkeley National Laboratory in California, USA, uncovers that changes in gene regulation shape the remarka-ble diversity of faces in birds and mammals.
A conserved blueprint for building the face
During embryonic development, facial growth is guided by signaling hubs known as devel-opmental organizers. These groups of cells act as local control centers, releasing signals that instruct nearby cells where to grow and what to become. In the face, one such organiz-er is located in the ectoderm, from where it sends such instructions by releasing mole-cules known as morphogens. Remarkably, many of the same morphogens are shared across birds and mammals, raising a fundamental question: if the signals are conserved, where does the diversity come from?
Evolution doesn’t change the tools; it modifies the instructions on how to use them
The researchers show that facial shape diversity arises primarily from changes in the non-coding DNA sequences that act as the switches controlling when and where genes are ex-pressed. “During embryonic development, many genes are used repeatedly in different tis-sues and at multiple stages,” says Dr. Markéta Kaucká. “If you change the gene itself, you risk breaking many processes and body parts at once. But by modifying the regulatory ele-ments that control where and when the gene is used, evolution can reshape specific fea-tures, such as the face, without compromising the whole organism.”
Evolution of cis-regulatory elements alters the patterns of conserved genes in developing embryos, creating species-specific signal maps. However, the researchers uncovered an additional and unexpected layer of evolutionary change. The most pronounced differences in gene regulation between mouse and chicken were not found in the signaling centers themselves, but in the mesenchymal cells, which receive instructions from signaling hubs to divide move to the right location, and adopt their final function.
“These cells eventually give rise, for instance, to cartilage and bone, acting as the primary builders of the facial skeleton, and dictating the facial shape. Our results suggest that fa-cial diversity is not only shaped by changes in how signals are produced, but also by how they are perceived by other cells,” says Stella Kyomen, PhD student and the first author of the study.
Link to human facial shape variation
The researchers also asked whether the same regulatory regions that control face shaping between species might play a role in human facial variation. To test this, they compared their data with large human genetic studies that link specific regions of the genome to dif-ferences in facial shape. They focused on regions of DNA that act as regulatory switches, controlling when and where genes are active during development.
Strikingly, many regulatory elements active in the developing face overlapped with genomic regions associated with human facial traits. “This suggests that the same regulatory mechanisms that evolution uses to generate diversity between species also contribute to variation within our own species,” says Stella Kyomen.
Collaborator Dr. Axel Visel adds: “These are fascinating data because they show that genes provide the blueprint, but it is the regulatory landscape that determines how that infor-mation is used. By integrating species-specific epigenomic data, we can now identify the broader conserved mechanisms that shape facial diversity across vertebrates.”
A new resource for studying facial evolution
This study generates a comprehensive dataset describing gene expression and regulatory activity in developing facial tissues, which is now openly available. The data are also ac-cessible through an interactive online database, providing a user-friendly resource for re-searchers exploring craniofacial development and evolution in birds and mammals.
“The generation of single-cell epigenomic data, especially from chicken facial tissues, will be an important resource for investigating craniofacial evolution,” says collaborator Dr. Laura Cook.
The interactive database can be accessed through the link:
https://www.evolbio.mpg.de/kyomen-cis-regulatory-evolution
Stella Marco Kyomen
Doktorandin
IMPRS EvolBio MPI
Max-Planck Forschungsgruppe Evolutionäre Entwicklungsdynamik
Kyomen, S., Seton, L.W.G., Cook, L.E., Escamilla-Vega, E., Murillo-Rincón, A.P., Jacobsen, A., Damatac II, A., Fortmann-Grote, C., Fuss, J., Visel, A., Kaucká, M. (2026). Cis-regulatory evo-lution shapes facial diversity in birds and mammals. Science Advances.
DOI: https://www.science.org/doi/10.1126/sciadv.aec2511
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