Study identifies the cellular origins of variation in human facial shapes
Early face positional programs are like "zip codes", marking the position of structures like the whiskers, nostrils and palate in the mouse embryo face.
© Andrea Patricia Murillo
To the Point
- Positional programs: Undifferentiated mesenchymal cells express positional programs: the cells know where they are before knowing what they will become. Genetich positional programs forecast the emergence of individual facial features
- Abnormalities: Mutations in discovered programs are linked to numerous craniofacial syndromes and facial abnormalities.
When we meet someone, we instinctively focus on their face because its shape is central to our identity and mutual recognition. But how does unique facial geometry arise? Which cells generate facial shape variability in humans, and how is our genetic information manifested in a localized manner so that we inherit a nose from one parent and lips from the other?
A new study by Markéta Kaucká and her team at the Max Planck Institute for Evolutionary Biology uncovers the cellular and molecular logic of face formation and shape acquisition. The team created the most detailed map to date of how the embryonic face develops, examining nearly 60,000 individual cells at different developmental stages in mice. By integrating the results with human genome-wide association studies, the researchers have linked genes to specific cells and the morphology of distinct facial features, revealing how the shape diversity arises.
At the heart of the discovery is the facial mesenchyme, undifferentiated cells that eventually build most of the facial bones. Before the facial skeleton forms, the undifferentiated mesenchymal cells already display distinct molecular profiles. In essence, the cells carry "positional programs," unique combinations of genes that act like molecular postal codes, marking where the nostrils, philtrum, or upper lip will emerge long before these structures exist. These positional programs also form the basis for the localized manifestation of our genetic information, enabling the composite inheritance of individual facial features from both parents.
Facial shape variability
Integrating human and mouse data shows that the mesenchyme, a mass of undifferentiated cells, is enriched in genes associated with human face shape variation
© Andrea Patricia Murillo
When the researchers integrated these cellular and molecular profiles with human genome-wide association studies of facial morphology, the connection was striking. Genes associated with normal human facial variation were highly enriched in the mesenchyme, indicating that these cells are the cellular source of human facial shape variability. This is contrary to the previous belief that ectoderm- or brain-derived signals orchestrate shaping the face. The established link between specific genetic variants, cells, and their positions in the forming face revealed that different cell populations have unique roles in forming various parts of the face.
This study provides valuable insights into the evolution of human facial shape and the origins of numerous craniofacial disorders. Alongside the reported findings, the team has created a publicly accessible online atlas that allows researchers in evolutionary and developmental biology, as well as medicine, to explore the developing face gene by gene and stage by stage.
