Meltrin β expressed in cardiac neural crest cells is required for ventricular septum formation of the heart
Meltrin β expressed in cardiac neural crest cells is required for ventricular septum formation of the heart
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DOI：
10.1016/j.ydbio.2006.10.037
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发表时间：
2007-03-01
影响因子：
2.7
通讯作者：
Sehara-Fujisawa, Atsuko
中科院分区：
文献类型：
--
作者：
Komatsu, Kouji;Wakatsuki, Shuji;Sehara-Fujisawa, Atsuko
心脏被膜性隔膜和瓣膜分为四个腔室。虽然有证据表明，膜隔的形成需要神经嵴细胞迁移到发育中的心脏，这些神经嵴细胞的功能意义的内膜垫，胚胎组织，产生膜附属物的发展，在很大程度上是未知的。Meltrin beta/ADAM 19蛋白酶区域缺陷的小鼠表现出室间隔缺损和瓣膜形成缺陷。在这项研究中，通过在内皮细胞或神经嵴细胞谱系中表达Meltrin β，我们表明Meltrin在神经嵴细胞中表达，而不是在内皮细胞中表达，这是形成室间隔和瓣膜所必需的。尽管Meltrin β缺陷型神经嵴细胞正常迁移到心脏中，但它们不能适当地融合近端流出道（OT）中的垫组织的左右脊，这导致形成室间隔的OT和AV垫的组装缺陷。这些结果在遗传学上证明了表达Meltrin β的心脏神经嵴细胞在触发近端OT垫融合和室间隔形成中的关键作用。(c)2006年爱思唯尔公司All rights reserved.
The heart is divided into four chambers by membranous septa and valves. Although evidence suggests that formation of the membranous septa requires migration of neural crest cells into the developing heart, the functional significance of these neural crest cells in the development of the endocardial cushion, an embryonic tissue that gives rise to the membranous appendages, is largely unknown. Mice defective in the protease region of Meltrin beta/ADAM19 show ventricular septal defects and defects in valve formation. In this study, by expressing Meltrin beta in either endothelial or neural crest cell lineages, we showed that Meltrin expressed in neural crest cells but not in endotbelial cells was required for formation of the ventricular septum and valves. Although Meltrin beta-deficient neural crest cells migrated into the heart normally, they could not properly fuse the right and left ridges of the cushion tissues in the proximal outflow tract (OT), and this led to defects in the assembly of the OT and AV cushions forming the ventricular septum. These results genetically demonstrated a critical role of cardiac neural crest cells expressing Meltrin beta in triggering fusion of the proximal OT cushions and in formation of the ventricular septum. (c) 2006 Elsevier Inc. All rights reserved.