Signaling intensities are indicated by color range. Our findings suggest that minor left-right differences in Bmp activity within the cardiac field may determine bi-phasic states: cardiac progenitor cells within the right cardiac cone are slightly more adhesive, and cells on the left side exhibit a slightly more motile character.Thus, cardiac left-right asymmetry may be explained by Nodal modulating an anti-motogenic Bmp activity.One particular focus of research is to characterize endocardial development.We use highly interdisciplinary approaches to analyze cardiac (both myocardial and endocardial) morphogenesis by combining expression analyses (deep sequencing; microarray studies), functional cell biological and genetic tools for tissue- or single cell level functional studies, modeling of single cell behaviors during cardiac morphogenesis, and pharmacological studies.
In a recent study, we were able to elucidate the molecular crosstalk between two Transforming Growth Factor-β (TGF-β) morphogens, Nodals and Bone morphogenetic proteins (Bmps), and to characterize their impact on left/right asymmetric development of the heart.We would like to understand: What are the signals that regulate the morphogenesis of myocardium and endocardium? traumpartner Kiel To what extent do these two tissues communicate during cardiac jogging and looping morphogenesis?One implication of these clonal studies is that changes in individual cell motility rates may impact the tissue displacement of larger coherent groups of cells.Figure 2:(A) Schematic diagram illustrating that the Nodal target Hyaluronan synthase 2 dampens Bmp activity within the left cardiac field which causes lower expression of non-muscle myosin II (NMII) and higher cardiac progenitor cell motility.
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These findings establish the endocardium as the flow-sensitive tissue in the heart with a key role in adapting chamber growth in response to the mechanical stimulus of blood flow.Taken together, our findings are indicative of dynamic interactions between the myocardium and endocardium that constantly attune cellular sizes and shapes, and thus cardiac chamber dimensions in response to physiological changes, the most important of which is blood flow.(B) Cross section through the cardiac field (myocardial cells marked green; F-actin, red).Molecular control of endocardial chamber morphogenesis In another study, we have recently analyzed the process of chamber morphogenesis of the endocardium (Dietrich et al., Dev. During heart development, the onset of heartbeat and blood flow coincides with a ballooning of the cardiac chambers (Figure 3). Initially the heart consists of only the outer myocardial and inner endocardial cell layers.
In our lab, we study the embryonic zebrafish heart, a relatively simple organ compared with its mammalian counterpart, to better understand the signaling events that instruct the assembly of the early heart tube.We also found that during cardiac ballooning stages, endocardial cells obtain distinct chamber- and inner-versus-outer-curvature-specific surface area sizes.Finally, we showed that the hemodynamic-sensitive transcription factor Krüppel-like factor 2a (Klf2a) is an important regulator of endocardial cell morphology.What determines the differentiation of endocardium into its different morphological derivatives such as cushion cells?In collaboration with clinical researchers, the group uses developmental genetics combined with cell biological and pharmacological approaches to develop animal models for human cardiovascular diseases.