Dr. Duncan B. Sparrow
Environmental influences on embryonic heart and vertebral formation
14th November, 1pm
ABSTRACT
Congenital heart disease (CHD) is the most common type of human birth defect with an incidence
of ~1% of live births. However, despite the rapid advances in research into the genetic causes of
rare diseases brought about by next-generation sequencing technologies, still only about 20% of
CHD cases have been shown to have a simple genetic cause. This suggests that many CHD cases
have multifactorial causes. One of these factors is likely to be environmental. Although embryonic
development is primarily controlled genetically, it has long been known that perturbation of the
environment in which the embryo forms can have a dramatic effect. For example, fetal under- or
over-nutrition can have long-lasting metabolic or epigenetic effects, manifesting in altered
physiology in adult life. By contrast, I have shown that one particular environmental insult, shortterm exposure of mouse embryos in utero to hypoxia, can have a transient effect and results in a
variety of specific gross morphological abnormalities including heart and vertebral defects. The
majority of the heart defects induced in this way are conotruncal in nature, and arise as a result of
interrupted development of the outflow tract and its precursor tissue, the second heart field. This
effect is mediated at the molecular level by an interruption of FGF signalling, and the penetrance
and severity of both heart and vertebral defects can be further exacerbated by genetic risk factors.
FGF signalling has key roles in many other processes during embryogenesis, including brain,
kidney, limb and craniofacial development. This raises the possibility that interactions between an
environmentally-induced reduction of FGF signalling, coupled with a genetic deficit, may play an
important role in the etiology of a wide range of “sporadic” human congenital defects.
BIOSKETCH
Dr. Duncan Sparrow is a Senior Research Scientist in the Division of Developmental and Stem Cell
Biology at the Victor Chang Cardiac Research Institute in Sydney, Australia. He did his PhD with Dr.
Julian Wells in the Biochemistry Department of Adelaide University, discovering a transcription
factor responsible for controlling the tissue-specific expression of the chicken histone H5 gene.
After completing his PhD, he joined Dr. Tim Mohun’s laboratory at the MRC National Institute for
Medical Research in Mill Hill where he applied his knowledge of transcription factor biology to
studying cardiogenesis and somitogenesis in Xenopus laevis. In mid-2000 he returned to Australia
to join Professor Sally Dunwoodie’s laboratory at the Victor Chang Cardiac Research Institute. Here
he has continued his studies of somitogenesis and cardiogenesis using a combination of mouse
embryology, human genetics and cell biology.