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Essential roles of Meltrin β (ADAM19) in heart development

By Kazuto Kurohara, Kouji Komatsu, Tomohiro Kurisaki, Aki Masuda, Naoki Irie, Masahide Asano, Katsuko Sudo, Yo-ichi Nabeshima, Yoichiro Iwakura and Atsuko Sehara-Fujisawa


AbstractMorphogenesis of the heart requires development of the endocardial cushion tissue that gives rise to the membranous septa and valves. Here we show that Meltrin β/ADAM19, a novel metalloprotease-disintegrin, participates in the development of the endocardial cushion. Mice lacking Meltrin β exhibit ventricular septal defect (VSD) and immature valves, and most of the animals die soon after birth. During development of the endocardial cushion, epithelial–mesenchymal transformation (EMT) of endocardial epithelial cells generates most of the cushion mesenchymes that constitute the main components of the septa and valves. Meltrin β is expressed in both the epithelia and the mesenchymes of the endocardial cushion. In the absence of Meltrin β, the cushion is small or thin in the septum-forming region and show poor remodeling of cardiac jelly components; both of these characteristics suggest impaired growth and differentiation of the endocardial cushion. When embryonic fibroblasts are cultured sparsely, Meltrin β-lacking cells exhibit aberrant ectodomain shedding of type I Neuregulin, one of the ErbB ligands expressed in endocardial cells. These results suggest the necessity of proteolytic regulation of ErbB ligands by Meltrin β for proper heart development

Publisher: Elsevier Inc.
Year: 2004
DOI identifier: 10.1016/j.ydbio.2003.10.021
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