Essential roles of Meltrin β (ADAM19) in heart development
| Autor: | Kazuto Kurohara, Kouji Komatsu, Tomohiro Kurisaki, Masahide Asano, Atsuko Sehara-Fujisawa, Yoichiro Iwakura, Naoki Irie, Katsuko Sudo, Yo-ichi Nabeshima, Aki Masuda |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Chromosomes
Artificial Bacterial congenital hereditary and neonatal diseases and abnormalities Disintegrins ErbB Blotting Western Morphogenesis Biology Embryonic and Fetal Development Mice Metalloprotease Knockout mouse Animals Endocardial cushion VSD Neuregulin Molecular Biology In Situ Hybridization DNA Primers Mice Knockout Metalloproteinase Cardiac Jelly Base Sequence Heart development Reverse Transcriptase Polymerase Chain Reaction Disintegrin Membrane Proteins Heart Anatomy Cell Biology Immunohistochemistry Embryonic stem cell Cell biology ADAM Proteins Blotting Southern Ectodomain embryonic structures Metalloproteases cardiovascular system Developmental Biology |
| Zdroj: | Developmental Biology. 267(1):14-28 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2003.10.021 |
| Popis: | Morphogenesis of the heart requires development of the endocardial cushion tissue that gives rise to the membranous septa and valves. Here we show that Meltrin beta/ADAM19, a novel metalloprotease-disintegrin, participates in the development of the endocardial cushion. Mice lacking Meltrin beta 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 beta is expressed in both the epithelia and the mesenchymes of the endocardial cushion. In the absence of Meltrin beta, 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 beta-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 beta for proper heart development. |
| Databáze: | OpenAIRE |
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