Until 2007, I was responsible for a group researching the structure of the normal and congenitally malformed heart, based initially at Royal Brompton Hospital, and from 1999 at Great Ormond Street Hospital for Children. Throughout this period, I was supported by the British Heart Foundation, and my colleagues and I elucidated the structure of not only the normal heart, but most congenital cardiac malformations. We also established the location of the conduction tissues in the setting of congenitally malformed hearts, and common arrhythmias, such as complete heart block, ventricular pre-excitation, and atrial fibrillation. At the start of my career, I had explored mechanisms of cardiac development, but had retreated from this line of research because of the inability to base findings on evidence as opposed to armchair speculation. Over the final years of my time at Great Ormond Street, I had returned to the field of cardiac development, working with colleagues at St George’s Hospital and the University of Amsterdam, and establishing a strong association with Deborah Henderson, who was then working at the Institute of Child Health in London. Subsequent to my enforced retirement from employment funded by the British Heart Foundation, therefore, I was delighted to accept a part-time appointment working primarily with Deborah Henderson and Bill Chaudhry at the Institute for Human Genetics.
In the Institute for Human Genetics, we now have access to a huge collection of human embryonic material. We are now using this resource to validate our previous studies of cardiac development in the normal and congenitally malformed murine heart. The discovery that all components of the heart are not present in the initial linear heart tube has revolutionised out understanding of not only normal, but also abnormal cardiac development. Over the past decade, it has been shown that, in the mouse heart, significant migrations of cells through both the arterial and venous poles are crucial for normal separation of the right and left sides. Thus, the vestibular spine, or dorsal mesenchymal protrusion, has been shown to play a key role in the separation of the mitral and tricuspid valves, with failure of formation of the spine correlated with the presence of a common atrioventricular junction. We now have evidence that a comparable arterial spine plays a similar role in separation of the common outflow tract into aortic and pulmonary channels. We are now replicating these findings in the human heart, using the human embryo database to compare our findings in human embryos known to be abnormal, such as those known to have Down’s syndrome.
Moorman A, Webb S, Brown NA, Lamers W, Anderson RH. Development of the heart: (1) Formation of the cardiac chambers and arterial trunks. Heart 2003;89:806-814.
Anderson RH, Webb S, Lamers W, Moorman A. Development of the heart: (2) Septation of the atriums and ventricles. Heart 2003;89:949-958.
Anderson RH, Webb S, Brown NA, Lamers W, Moorman A. Development of the heart: (3) Formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks. Heart 2003;89:1110-1118.
Deborah Henderson BSc PhD
Professor of Cardiac Development, BHF Basic Science Lecturer
Susan Lindsay BSc MBA PhD
Professor of Human Developmental Genetics
Bill Chaudhry MB BS MRCP PhD
Senior Lecturer in Biophysics and Cardiac Development
Helen Arthur BSc PhD
Senior Lecturer in Molecular Cardiovascular Medicine
and British Heart Foundation Senior Basic Science Research Fellow
Helen Phillips BSc, PhD
Newcastle University Faculty of Medical Sciences Fellow
Alina Andras, BSC, PhD
Newcastle Hospitals Trust JRE Research Associate