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Cardiac development and genetics

The zebrafish model is used to study the genetics of heart diseases. By forward genetic screening and reverse-genetics techniques in zebrafish we aim to identify novel genes that have important functions during vertebrate heart development and function and can contribute to cardiac diseases in humans.

Heart development
The circulatory system of vertebrates has various necessary functions throughout embryonic and adult life. A wide range of congenital and acquired human diseases are associated with pathological conditions in heart formation. Since the signalling mechanisms affected in these diseases are the same mechanisms that occur during embryonic heart development, their study is a subject of great interest and relevance.

The zebrafish offers several distinct advantages as a genetic and embryological model system for these studies. Their external fertilization, rapid development and optical clarity makes them very suitable for studying important cellular processes during embryonic heart development such as cell migration, proliferation and differentiation. We use forward and reverse genetic tools to identify novel genes that are required for normal heart development and use in situ hybridization, antibody stainings and confocal micrsocopy to study the function those genes.

Genetics of human congenital heart defects
Congenital heart defect (CHD) is the most common human birth defect and the leading cause of death in the first year of life. In the Netherlands , 1500 children with CHD are born every year. Although many patients born with a CHD have a positive family history, there are only a few cases in which the genetic defect causing the malformation has been identified. We are screening CHD patients for genetic variations and are testing the effect of novel variations on protein function in vitro and in vivo. Hopefully this will lead to a better understanding of what can cause human CHDs. In addition, we exploit GWAS and exome-sequencing data for cardiovasculare diseases to better understand the causes and mechanisms of the disease.

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image description

Live imaging of cardiac tube morphogenesis in zebrafish.
Shown are reconstructions of confocal Z-stacks during three different time points of heart morphogenesis. Imageing was performed in a living zebrafish embryo expressing GFP specifically in cardiomyocytes. The colored dots mark individual cells to visualize their migration paths resulting in a clockwise rotation of the heart (indicated by the white line).