Comment: Scientists are detectives. We have to separate direct from circumstantial evidence, carry out our own enquiries and also make sense of the statements provided by other laboratories, who may or may not be reliable witnesses. Jonathan Butcher’s lab is pursuing new lines of enquiry relating to the relationship between mechanical forces and genetic pathways and unearthing novel clues about normal and abnormal valve morphogenesis. His recent publication convincingly implicates YAP in mechanotransduction during atrioventricular valve morphogenesis.
Importantly, Jonathan’s team evaluate several different types of mechanical force relevant in the developing heart, including unidirectional shear, oscillatory shear, hydrostatic compressive and tractional stresses. This work, through a range of different experiments, provides solid evidence for a mechanism for linking AV valve development to mechanical forces through the YAP pathway.
However there are a couple of points that we might need to clarify when we question Professor Butcher. Firstly, what is happening in the forming aortic and pulmonary valves? Is this mechanism also active here - and if not, why not? Secondly, is there any evidence that the YAP pathway should be held directly responsible for human congenital heart malformations or is it an innocent bystander, forced to participate in the crimes of other corrupted developmental processes?
This commentary is inspired by the award winning UK television detective series “Vera”, which is filmed in Newcastle upon Tyne and Northumberland. I recommend Jonathan’s paper – and the TV series
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