DISTRIBUTION OF ENDOGLIN IN EARLY HUMAN-DEVELOPMENT REVEALS HIGH-LEVELS ON ENDOCARDIAL CUSHION TISSUE MESENCHYME DURING VALVE FORMATION

Endoglin is a component of the receptor complex for transforming growt h factor (TGF)-beta 1 and TGF-beta 3. We analysed its expression by im munohistochemistry in human embryos at 4-8 weeks of gestation and in h earts ranging from 4-13 weeks old. We compared endoglin distribution w ith that of TGF-beta receptors type I (T beta R-I), type II (T beta R- II) and betaglycan. Endoglin was found on endothelial cells in all tis sues examined, consistent with its expression in adult blood vessels. T beta R-I, T beta R-II and betaglycan were observed on most cell type s and had an overall similar pattern of distribution. Endoglin was det ected on the endocardium as early as 4 weeks, but was absent from myoc ardium. It was present at high levels on the endocardial cushion tissu e mesenchyme from 5-8 weeks' gestation, during heart septation and val ve formation, and subsequently decreased as the valves matured. Endogl in expression in heart extracts was confirmed by Western blot analysis . T beta R-I, T beta R-II and betaglycan were mostly found on cardiac myocytes, but were detectable at law levels on endocardium. They were expressed transiently on cushion mesenchyme, albeit at much lower leve ls than endoglin. All four components of the TGF-beta receptor complex were detected by RT-PCR in embryonic heart. Thus transient up-regulat ion of the components of the TGF-beta receptor complex, and particular ly of endoglin, is associated with heart septation and valve formation during early human development.