Does your face reveal what’s in your heart? It might – even more than you know. Take, for instance, a common group of birth defects – forms of a disorder called DiGeorge syndrome. Around one in 4000 is born with this syndrome, which arises from a deletion of a short segment of chromosome 22. Among other problems, this deletion nearly always involves deformations in both the face and the heart.
The Institute’s Prof. Eldad Tzahor had already shown that face and heart go together: Very early on in the developing embryo, the progenitor cells that will become heart and facial muscles start out together in the same “classroom” – a small area in the neck region. It’s not just incidental: It turns out that these cells not only arise from the same population, they need to “talk” to one another before they can move off to their respective places in the developing embryo.
But this didn’t explain why a single chromosomal deletion can cause a whole range of problems, from relatively mild defects to debilitating ones that require urgent intervention at birth. Tzahor and his student, Itamar Harel began looking for the answer in transcription factors — the proteins that initially control genetic activity.
After identifying a number of relevant transcription factors, Tzahor, Harel and their collaborators around the world spent months developing and testing knockout mice that would reveal, in detail, the functions of these regulatory proteins in the development of the heart and face progenitors. Even more challenging was the creation of double-knock out embryos, missing two of the transcription factors.
Their ultimate finding was that the transcription factors form a network. There are upstream and downstream effects, but also sideways and indirect interactions. And that network tends to be at least partly self- correcting. When two transcriptions factors were lacking, the network’s outputs collapse, but with only one missing, others apparently stepped in to pick up some of the slack, resulting in a few “slip-ups,” but more or less complete hearts and facial muscles.
And yes, they revealed that, at least for those with DiGeorge syndrome, a face can tell something about the heart. They found that knockouts of specific transcription factors that were not previously linked to Digeorge were tied to distinctive combinations of facial muscle and cardiac defects resemble the congenital defects in babies. Tzahor and Harel suggest that certain birth defects in a newborn’s face could tell doctors to check for a corresponding heart problem.