Novel genes, pathways and processes involved in arterial valve development in mouse and man

Most of what we understand about the development of the arterial (aortic and pulmonary) valves is extrapolated from investigations of the atrioventricular valves in animal models, with surprisingly little specifically known about how the arterial valves develop in mouse, and even less in human. Over several years we have been uncovering novel mechanisms that play important roles in the formation and remodelling of the mouse arterial valve leaflets, and then investigating whether the same processes occur in human embryos. I will show new data about some of these mechanisms, genes and signalling pathways, highlighting similarities and differences between mouse and human embryos, and relating this to malformations and diseases that affect the arterial valves.

SPEAK BIOGRAPHY

Deborah Henderson is a cardiac developmental biologist who focuses on understanding the morphogenetic mechanisms that underpin formation of the heart and great vessels and that are disrupted to result in congenital heart defects (CHD). She trained as a developmental biologist at the Institute of Child Health, UCL, before moving to Newcastle University in 2002 to establish an independent research team. Since then she has led a research team using a range or model systems and approaches. For example, genomic studies in rigorously phenotyped patients are being used to identify gene variants that are associated with specific congenital heart defects, such as hypoplastic left heart syndrome. Mouse and zebrafish are then used as models to investigate how and why specific malformations arise – a particular interest in this respect is bicuspid aortic valve. Understanding the roles that different progenitor populations, particularly the second heart field and neural crest cells, play in formation, both normal and pathogenic, of the valves and septa of the developing heart, is a major goal. This research extends to understanding how minor cardiovascular anomalies, particularly those affecting the aortic valve and ascending aorta, can predispose to heart disease in later life. She is an active member of the ESC Working Group of Development, Anatomy and Pathology, where she served as Nucleus Chair from 2016-18.

Deborah is also the Newcastle Director of the Human Developmental Biology Resource (hdbr.org), a human embryonic and fetal biobank that supports research projects around the world.