Illuminating Craniofacial Development | TS Digest


Craniofacial anomalies are some of the most common birth defects and can severely impact individuals’ lives, potentially compromising the ability to speak, eat, and even breathe. Some of these disorders, known as neurocristopathies, arise from perturbations of the delicate developmental choreography of the neural crest cells. Paul Trainor, a developmental biologist at the Stowers Institute for Medical Research, hopes that determining exactly where, when, and why these cells go awry will inspire new strategies to prevent these disorders.

     Paul Trainor wears a blue shirt and smiles at the camera.

Paul Trainor studies neural crest cells and craniofacial development at the Stowers Institute for Medical Research.

Paul Trainor

What drew you to study neural crest cells?

Neural crest cells are a fascinating population. These cells make most of the bone, cartilage, and connective tissue of the head and face. As they are formed early in embryo development, their proliferation, migration, and differentiation are prone to both genetic and environmental insults. Studying neural crest cells allows me to ask fundamental questions about development, but our research also has potential clinical significance.

How could studying these developmental processes help inform treatments? 

Once we understand the genetic and the molecular processes that cause a specific disorder, we can start to figure out how to correct those processes and prevent the disorder. For example, we know that one disorder, called Treacher Collins syndrome, can be caused by TCOF1 mutations.1 This gene plays a key role in ribosome biogenesis and DNA damage repair. We found that the high levels of oxidative stress naturally experienced by neural crest cells during development can damage DNA; if there are problems with TCOF1, the cell may not be able to repair the damage and will die. In human embryos, we can’t fix the gene, but we might be able to reduce DNA damage. In mice, we showed that antioxidant administration during pregnancy reduced oxidative stress induced DNA damage and increased cell survival, ultimately reducing craniofacial abnormalities.2  

This interview has been edited for length and clarity.

References

  1. The Treacher Collins Syndrome Collaborative Group. Nat Genet. 1996;12(2):130-136.
  2. Sakai D et al. Nat Commun. 2016;7(1):10328.

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