Sox4 mediates Tbx3 transcriptional regulation of the gap junction protein Cx43

Tbx3, a T-box transcription factor, regulates key steps in development of the heart and other organ systems. Here, we identify Sox4 as an interacting partner of Tbx3. Pull-down and nuclear retention assays verify this interaction and in situ hybridization reveals Tbx3 and Sox4 to co-localize extensively in the embryo including the atrioventricular and outflow tract cushion mesenchyme and a small area of interventricular myocardium. Tbx3, SOX4, and SOX2 ChIP data, identify a region in intron 1 of Gja1 bound by all tree proteins and subsequent ChIP experiments verify that this sequence is bound, in vivo, in the developing heart. In a luciferase reporter assay, this element displays a synergistic antagonistic response to co-transfection of Tbx3 and Sox4 and in vivo, in zebrafish, drives expression of a reporter in the heart, confirming its function as a cardiac enhancer. Mechanistically, we postulate that Sox4 is a mediator of Tbx3 transcriptional activity

Concepts of Cardiac Development in Retrospect

Recent research, enabled by powerful molecular techniques, has revolutionized our concepts of cardiac development. It was firmly established that the early heart tube gives rise to the left ventricle only, and that the remainder of the myocardium is recruited from surrounding mesoderm during subsequent development. Also, the cardiac chambers were shown not to be derived from the entire looping heart tube, but only from the myocardium at its outer curvatures. Intriguingly, many years ago, classic experimental embryological studies reached very similar conclusions. However, with the current scientific emphasis on molecular mechanisms, old morphological insights became underexposed. Since cardiac development occurs in an architecturally complex and dynamic fashion, molecular insights can only fully be exploited when placed in a proper morphological context. In this communication we present excerpts of important embryological studies of the pioneers of experimental cardiac embryology of the previous century, to relate insights from the past to current observations

A theory of surface enrichment in ordered alloys

A simple theory was developed to explain exptl. data on surface enrichment in Pt3Sn. The computed surface enrichment is in accord with exptl. findings. The theory predicts that in the Pt3Sn system enrichment occurs by interchange of atoms of the element with the lower heat of sublimation from the layer just below the surface with atoms of the other element in the surface. Arguments are presented why an expt. performed on Au-Cu alloys should be capable of verifying an assumption basic to the theory