Endocardium is necessary for cardiomyocyte movement during heart tube assembly.
ABSTRACT Embryonic heart formation requires the union of bilateral populations of cardiomyocytes and their reorganization into a simple tube. Little is known about the morphogenetic mechanisms that coordinate assembly of the heart tube and determine its dimensions. Using time-lapse confocal microscopy to track individual cardiomyocyte movements in the zebrafish embryo, we identify two morphologically and genetically separable phases of cell movement that coordinate heart tube assembly. First, all cardiomyocytes undergo coherent medial movement. Next, peripherally located cardiomyocytes change their direction of movement, angling toward the endocardial precursors and thereby establishing the initial circumference of the nascent heart tube. These two phases of cardiomyocyte behavior are independently regulated. Furthermore, we find that myocardial-endocardial interactions influence the second phase by regulating the induction, direction and duration of cardiomyocyte movement. Thus, the endocardium plays a crucial early role in cardiac morphogenesis, organizing cardiomyocytes into a configuration appropriate for heart tube assembly. Together, our data reveal a dynamic cellular mechanism by which tissue interactions establish organ architecture.
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ABSTRACT: The endocardium forms the inner lining of the heart tube, where it enables blood flow and also interacts with the myocardium during the formation of valves and trabeculae. Although a number of studies have identified regulators of the morphogenesis of the myocardium, relatively little is known about the molecules that control endocardial morphogenesis. Prior work has implicated the bHLH transcription factor Tal1 in endocardial tube formation: in zebrafish embryos lacking Tal1, endocardial cells form a disorganized mass within the ventricle and do not populate the atrium. Through blastomere transplantation, we find that tal1 plays a cell-autonomous role in regulating endocardial extension, suggesting that Tal1 activity influences the behavior of individual endocardial cells. The defects in endocardial behavior in tal1-deficient embryos originate during the earliest steps of endocardial morphogenesis: tal1-deficient endocardial cells fail to generate a cohesive monolayer at the midline and instead pack tightly together into a multi-layered aggregate. Moreover, the tight junction protein ZO-1 is mislocalized in the tal1-deficient endocardium, indicating a defect in intercellular junction formation. In addition, we find that the tal1-deficient endocardium fails to maintain its identity; over time, a progressively increasing number of tal1-deficient endocardial cells initiate myocardial gene expression. However, the onset of defects in intercellular junction formation precedes the onset of ectopic myocardial gene expression in the tal1-deficient endocardium. We therefore propose a model in which Tal1 has distinct roles in regulating the formation of endocardial intercellular junctions and maintaining endocardial identity.Developmental Biology 09/2013; · 3.87 Impact Factor
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ABSTRACT: The T-box transcription factor Tbx5 (Tbx5a in zebrafish) plays a crucial role in the formation of cardiac chambers in a dose-dependent manner. Its deregulation leads to congenital heart disease. However, little is known regarding its regulation. Here we isolate a zebrafish mutant with heart malformations, called 34c. The affected gene is identified as kctd10, a member of the potassium channel tetramerization domain (KCTD)-containing family. In the mutant, the expressions of the atrioventricular canal marker genes, such as tbx2b, hyaluronan synthase 2 (has2), notch1b and bmp4, are changed. The knockdown of tbx5 rescues the ectopic expression of has2, and knockdown of either tbx5a or has2 alleviates the heart defects. We show that Kctd10 directly binds to Tbx5 to repress its transcriptional activity. Our results reveal a new essential factor for cardiac development and suggest that KCTD10 could be considered as a new causative gene of congenital heart disease.Nature Communications 01/2014; 5:3153. · 10.74 Impact Factor