Margaret Buckingham: Studying the Choreography of Cardiogenesis

Abstract

Were it not for an experiment that had apparently gone wrong, Margaret Buckingham, a professor in the department of developmental biology at the Pasteur Institute in Paris, France, may have never discovered her most important contribution to the field of cardiology. When Buckingham and her colleague Robert Kelly saw an unexpected expression pattern of a myosin transgene in engineered mice, they did not scrap the experiment and start over, but instead they investigated more closely. The transgene, they later discovered, had integrated into the gene for fibroblast growth factor 10 ( Fgf10 ) and had inadvertently become an excellent marker for a population of heart progenitor cells. Until that point, it had been assumed that the mammalian heart arose from one population, or field, of embryonic cells. The work of Buckingham and Kelly showed that there were, in fact, two quite separate heart fields, deriving from two myocardial cell lineages.1–3 These discoveries changed the way biologists thought about normal heart development and about how congenital heart defects might arise. Margaret Buckingham. Buckingham said, in a recent interview with Circulation Research , that having a keen eye and not immediately dismissing aberrant results as artifacts are two important aspects of scientific endeavor. So, too, she added, is an unwavering perseverance. In addition to her heart development work, Buckingham studies skeletal muscle development. One of the key differences between the two muscle types, she showed, was in the upstream cell fate decision-making factors. One of her other major discoveries was that a family of transcription factors encoded by Pax genes drives the cell fate choices in the early embryo that eventually lead to skeletal muscle formation.4,5 In both the heart and skeletal muscle fields, therefore, Buckingham has been, and continues to be, a leading light. ### Where Did You Grow Up? I spent the …