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For non-scientists |
Congenital heart diseases are structural defects in the heart that are present at birth - this includes holes in the heart, abnormal heart valves, and improper connection of the blood vessels to the heart. They are the most common birth defects - around 1% of babies are born with heart diseases, and they often require immediate surgery and in some cases lifelong care.
These structural problems in the heart occur because the heart doesn't form properly while the baby is developing in the womb. To understand a disease, you need to understand it's origin. We are interested in finding out what genes are required for normal development of the heart, and why these genes are important. We use the zebrafish to study the early stages of heart development. Zebrafish are a great model organism to study the heart - early development of the heart happens the same in a fish as it does in humans, and over 80% of disease-causing genes in human are also found in zebrafish, meaning we can directly see how they affect heart development! Zebrafish embryos also develop very quickly, and are transparent so we can visualise live how the heart grows and folds and changes during embryo development. We are particularly interested in how the left-right asymmetry of our bodies is important for normal heart formation, and how the scaffolding of the cell (the 'cytoskeleton') helps cells in the heart work together to allow it to change shape and take on it's proper form. |
Expert summary |
During embryonic development, the heart undergoes significant looping morphogenesis, transitioning from a linear tube to a looped heart. This process is vital for ensuring proper chamber alignment (and subsequent septation), normal flow and valvulogenesis, and correct formation of the inflow and outflow tracts of the heart. Disruption to this complex series of events results in a spectrum of congenital heart defects, therefore understanding how these processes occur is vital to furthering out understanding of cardiac diseases.
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Heart looping occurs relatively quickly, and is subject to the three main inputs:
Embryonic left-right asymmetry Tissue rearrangement Growth of the heart |
We have previously demonstrated that embryonic left=right asymmetry is important in promoting directional heart morphogenesis, but that the heart also retains the ability to undergo looping morphogenesis without external (asymmetric) stimuli (tissue-intrinsic looping). Using a combination of heart explant and pharmacological techniques we and others have shown that the inherent ability of the heart to undergo morphogenesis is dependent upon specific cytoskeletal interactions.
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