The Investigation of Bmp Modulators during Cardiac Jogging in Zebrafish

Abstract

The failure to establish left-right (L/R) asymmetry in the heart leads to congenital heart defects in humans. In zebrafish, TGFβ signaling pathways Nodal and Bmp are asymmetrically expressed and are important in L/R patterning during heart morphogenesis. Directed by Nodal signaling, left-sided myocardial cell migration rates lead to a process called cardiac jogging, which will result in the formation of the cardiac tube. Microarray results were analyzed to find Nodal targets that were upregulated in the heart and may contribute to asymmetric cardiac jogging. bmper and bambia were chosen be- cause they are known Bmp modulators, suggesting the communication of Nodal and Bmp signaling during cardiac jogging. These genes were previously unstudied during this process. Spatial expression patterns of the target genes reveal their expression in the heart and the possible downregulation of bmper by Nodal. Quantitative levels of target gene expression show that bmper is downregulated by Nodal. However, bambia levels are un- changed, perhaps because the technique used was not sensitive enough to detect heart- specific changes due to wider expression in the embryo. This study suggests that Nodal is perhaps downregulating bmper and upregulating bambia to modulate Bmp signaling in order to promote left-sided cardiac jogging and the formation of a properly functioning heart.