Paul Trainor investigates the molecular interactions during normal mammalian development that regulate cranial and facial development in his lab at the Stowers Institute for Medical Research in Kansas City, Missouri. Anomalies in craniofacial development manifest one-third of all congenital birth defects in humans, and knowing exactly what happens in normal development is key to understanding how these defects arise.

Neural crest cells are a migratory cell population formed early during embryogenesis that are central to craniofacial development. They give rise to most of the bone, cartilage, connective and peripheral nerve tissues in the head and face, so not surprisingly then, abnormal patterning of these cells in the embryo is behind most craniofacial defects.

“In simplest terms, we think of most craniofacial birth defects as being a neural crest cell-related problem,” Trainor says. “This can be a formation, migration or differentiation problem, and depending on what phase of crest cell development is disrupted, you can end up with very different craniofacial anomalies.”

These different defects produce diverse facial phenotypes and complications of the phenotype, and accordingly, quite different syndromes in humans. “To understand any of these syndromes, or in fact to start thinking about ways to prevent them and exactly when to intervene, we first need to understand the origin of the problem in each case, and then the pathogenesis of that syndrome.”

A disorder of craniofacial development that Trainor is particularly interested in is Treacher Collins syndrome. “We work on it as an example of how understanding the basic biology of a problem using animal models can explain a lot of what is going on in the human condition,” he says.

This rare human condition is characterised by developmental anomalies such as hypoplasia of the facial bones, middle and external ear defects and cleft palate. Most of the structures affected in this syndrome arise, at least in part, from cranial neural crest cells, and the syndrome seems to involve a problem early on in crest cell formation.

The gene mutation that causes Treacher Collins syndrome is in the Tcof1 gene, which encodes the nucleolar protein Treacle 1. Using a combination of lineage tracing, cell transplantation and cDNA library screening experiments, Trainor is currently investigating the role of Tcof1 in neural crest cell development for a clue to the origins of Treacher Collins syndrome as well as possible avenues for prevention and repair.