The expression of Jagged1 in the developing mammalian heart correlates with cardiovascular disease in Alagille syndrome

The establishment of the cardiovascular system represents an early, critica l event essential for normal embryonic development, and defects in cardiova scular development are a frequent cause of both in utero and neonatal demis e, Congenital cardiovascular malformations, the most frequent birth defect, can occur as isolated events, but are frequently presented clinically with in the context of a constellation of defects that involve multiple organs a nd that define a specific syndrome. In addition, defects can be a primary e ffect of gene mutations or result from secondary effects of altered cardiac physiology, Alagille syndrome (AGS) is an autosomal dominant disorder char acterized by developmental abnormalities of the heart, liver, eye, skeleton and kidney. Congenital heart defects, the majority of which affect the rig ht-sided or pulmonary circulation, contribute significantly to mortality in AGS patients. Recently, mutations in Jagged1(JAG1), a conserved gene of th e Notch intercellular signaling pathway, have been found to cause AGS, In o rder to begin to delineate the role of JAG1 in normal heart development we have studied the expression pattern of JAG1 in both the murine and human em bryonic heart and vascular system, Here, we demonstrate that JAG1 is expres sed in the developing heart and multiple associated vascular structures in a pattern that correlates with the congenital cardiovascular defects observ ed in AGS, These data are consistent with an important role for JAG1 and No tch signaling in early mammalian cardiac development.