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.

Dependence of cardiac trabeculation on neuregulin signaling and blood flow in zebrafish

“…Embryos shown represent the most common morphology that was observed in at least 20 wild-type embryos, at least 15 clo mutant embryos, at least 15 AG1478-treated embryos, and at least 5 wea mutant embryos at each stage examined. In each stable transgenic line, we found considerable variability in the level of transgene expression among individual cardiomyocytes; this degree of variegation is compatible with previous observations of transgenes driven by the myl7 promoter and is presumably due to epigenetic silencing (e.g., Holtzman et al, 2007).…”

Endoderm convergence controls subduction of the myocardial precursors during heart-tube formation

“…2), which is earlier than when myocardial precursors have been reported to migrate to the midline (16-20 s) (Holtzman et al, 2007). Moreover, our data indicate that the endoderm expands slightly from 18-20 s (Fig.…”

Arterial and venous vessels are required for modulating developmental relocalization and laterality of the interrenal tissue in zebrafish

“…While the budding of embryonic liver and pancreas from the developing gut occurs at the level posterior to the interrenal tissue at the midtrunk, the direction of outgrowth as well as laterality for these two digestive organs are unaffected in the endothelium-free clo mutant (Field et al, 2003a,b). The initial medial movement of cardiomyocytes was not affected in clo, yet the absence of endocardium leads to a later defect in the assembly and elongation of the heart tube (Holtzman et al, 2007). Nevertheless, laterality of the heart tube during its assembly is not aberrant in clo.…”

“…Also, a vast array of mutants and morphants manifesting various types of vascular disorders has allowed a detailed genetic dissection of endothelial signals that modulate organogenesis. For example, in the developing zebrafish embryo, endothelium has been found to regulate cardiomyocyte movement during heart tube assembly (Holtzman et al, 2007), to provide guidance cues for defining the position of the thyroid gland (Alt et al, 2006), and to regulate the apicobasal polarization of hepatocytes (Sakaguchi et al, 2008). Furthermore, endotheliumderived signals play morphogenetic roles for the embryonic renal and interrenal organs (Serluca et al, 2002;Liu and Guo, 2006), while these two organs develop in a highly parallel manner.…”