The human body consists of hundreds, perhaps thousands of different types of cells, each with different morphologies and functions, despite having the same genome. This diversity is created by gene... Show moreThe human body consists of hundreds, perhaps thousands of different types of cells, each with different morphologies and functions, despite having the same genome. This diversity is created by gene regulation, a set of mechanisms that determine, which genes are used to make proteins and which genes are kept silent. During embryonic development, gene are turned on and off in a tightly orchestrated manner, to make sure that the right cell type is created at the right time and place.In this thesis we report several studies pertaining to gene regulation in embryonic development. Each of the four chapters will cover a different layer of the gene regulation toolbox: gene inactivation by DNA methylation, transcriptional regulation in the developing kidney, regulation of protein turnover and translational regulation through micro-RNAs. Together, these studies provide a refined understanding of the crucial role of gene regulation for embryonic development. Show less
The aim of this thesis was to further characterize the right ventricle within three different fields of cardiovascular research: 1. Embryonic development, 2: Non-invasive right ventricular imaging,... Show moreThe aim of this thesis was to further characterize the right ventricle within three different fields of cardiovascular research: 1. Embryonic development, 2: Non-invasive right ventricular imaging, 3: Right ventricular electrocardiography. In part I, several aspects of embryonic development, relevant for normal right ventricular morphology and function are investigated. In chapter 2, a novel concept for normal development of the right ventricular outflow tract is introduced. In chapter 3, the potential relevance of epicardium-derived cells for the difference between left and right ventricular morphology is discussed. Non-invasive imaging techniques are evaluated in part II. In chapter 4, the use of conventional semi-quantitative measurement of right ventricular function in patients with transposition of the great arteries is analyzed. The relevance of abnormal response to stress, measured with cardiovascular magnetic resonance imaging, is investigated in chapter 5. Chapters 6-8 demonstrate how strain measurement can be used in various types of (suspected) right ventricular disease. In part III, both conventional electrocardiography as well as computerized vectorcardiography is described in patients with right v entricular disease. A case-study of conventional electrocardiographic assessment of right ventricular pressure overload is provided in chapter 9. The prognostic value of QRS duration in patients with tetralogy of Fallot who undergo pulmonary valve replacement, is demonstrated in chapter 10. Chapter 11 and 12 discuss the application of ECG-derived vectorcardiography in normal subjects and suspected pulmonary arterial hypertension patients Show less
Versieren, K.; Jeught, M. van der; O'Leary, T.; Duggal, G.; Gerris, J.; Lopes, S.C.D.; ... ; Sutter, P. de 2012
In developmental biology, the expression of genes is studied to understand development, phenotypes and to construct models to understand disease. In this thesis, we explore and validate biological... Show moreIn developmental biology, the expression of genes is studied to understand development, phenotypes and to construct models to understand disease. In this thesis, we explore and validate biological as well as computerized tools, to address research questions in developmental biology. Based on these techniques, we developed a workflow to generate a large number of 3D spatio-temporal patterns of gene expression. Though several techniques for gene expression analysis are available, most spatial gene expression data are only in 2D. In order to study gene expression and differentiation of structures during development at the same time, both spatial 3D information, and temporal data are essential. These spatio-temporal patterns of gene expression have to be generated. To that end, we have developed a workflow based on fluorescent in situ hybridization (FISH) (ZebraFISH;), confocal laser scanning microscopy (CLSM) and subsequent three-dimensional modeling with, in our case, TDR-3Dbase software- resulting in a large amount of 3D spatio-temporal patterns of gene expression, obtained in a straightforward and non-destructive manner. In the work described in this thesis, we applied the workflow to 30 genes in 5 developmental processes. 3D modeling and data mining software are used to analyse gene expression patterns in zebrafish embryos and across species Show less
