For a study appearing in Nature Communications, researchers at the University College London and elsewhere investigate what combination of genetic and environmental factors come into play to cause cleft lip/palate (CLP), the most common craniofacial malformation. While previous studies have found genetic variants associated with the condition, those findings had failed to completely explain CLP heritability. In short, not everyone with the variants developed CLP. One of the genes linked to CLP is CDH1 (E-cadherin), a member of the cadherin-catenin complex. When researchers studied families who carry this mutation, they noted that not everyone with the mutation develops a cleft lip. They reproduced this mutation in mice and frogs and noticed that the animals carrying the mutation developed CLP only when they were also exposed to inflammation-causing environmental factors. They later also found similar effects in human stem cells with both the mutation and inflammation. "We have hypothesized CDH1/E cadherin as a central node affected by pro-inflammatory activation and our results corroborate this idea," the authors wrote. They however cautioned that proinflammatory activation might affect other genes and pathways that could contribute to the development of CLP.