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• The study identifies the cellular origins of human facial shape variation.
• Undifferentiated mesenchymal cells carry positional programs – they know where they are before knowing what they will become.
• These positional programs forecast the emergence of individual facial features.
• Mutations in these programs are linked to numerous craniofacial syndromes and facial abnormalities.
Why do no two human faces look quite the same? Although we all follow the same biological blueprint, our features — the curve of a lip, the angle of a nose, the breadth of a jaw — diverge in endlessly subtle ways. A team of researchers from the Max Planck Institute for Evolutionary Biology in Plön, Germany, has uncovered a crucial piece of that long-standing puzzle.
In a study by the Research Group Evolutionary Developmental Dynamics, led by Dr Markéta Kaucká, the team has produced the most detailed account to date of how the face takes shape in the embryo. By examining nearly 60,000 individual murine cells across multiple developmental stages and integrating these findings with human genome-wide association studies, the scientists have traced human facial diversity back to its cellular foundations.
Their results point to an unexpected architect: the facial mesenchyme, a population of undifferentiated cells that eventually forms much of the facial skeleton. Long before any visible structure appears, these cells display distinct molecular identities — what the authors describe as “positional programmes.” These patterns of gene activity act like molecular postal codes, marking where the philtrum, the nostrils or the upper lip will one day emerge.
“Before the face becomes the face, the cells already know exactly where they are,” Dr Kaucká said.
The study suggests that these positional programmes are the underlying reason why we can inherit a nose from one parent and the shape of a mouth from the other. By linking these molecular signatures with human genetic variants associated with facial form, the team discovered that genes influencing normal facial variation are particularly active in these mesenchymal cells. This finding challenges the long-held assumption that signals from the ectoderm or the developing brain primarily sculpt the face.
Instead, what emerges is a picture of finely tuned cellular geography: distinct clusters of mesenchymal cells carry out dedicated roles in constructing specific regions of the face.
Beyond shedding light on the evolution of human facial diversity, the work also provides valuable insights into numerous craniofacial disorders — congenital conditions that arise when these positional programmes are disrupted. To enable further exploration, the team has released an online atlas that charts the developing face gene by gene and stage by stage. (https://www.evolbio.mpg.de/murillo-seton2025)
Published in Nature Communications, the study lays the groundwork for a more complete understanding of how identity itself — the thing we instinctively search for when we look at one another — begins.
Murillo-Rincón A.P., Seton L.W. G., Escamilla-Vega E., Damatac II A., Fuß J., Fortmann-Grote C. & Kaucká M.
Positional programmes in early murine facial development and their role in human facial shape variability.
Nat Commun 16, 10112 (2025). https://doi.org/10.1038/s41467-025-66017-y
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