Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish.
Nephronectin regulates atrioventricular canal differentiation via Bmp4-Has2 signaling in zebrafish.
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DOI：
10.1242/dev.067454
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发表时间：
2011-10
期刊：
影响因子：
--
通讯作者：
Engel FB
中科院分区：
文献类型：
--
作者：
Patra C;Diehl F;Ferrazzi F;van Amerongen MJ;Novoyatleva T;Schaefer L;Mühlfeld C;Jungblut B;Engel FB
细胞外基质对器官形成至关重要。它是一种复杂的动态组分，通过调节活性、生物利用度和生长因子对细胞表面受体的呈递来调节细胞行为。在这里，我们确定的作用，细胞外基质蛋白肾结合蛋白（Npnt）在心脏发育中使用斑马鱼模型系统。脊椎动物的心脏形成为一个线性管，其中心肌和内膜被称为心胶质的细胞外基质层隔开。在心脏发育过程中，心脏胶状物在房室（AV）通道处膨胀，这先于瓣膜形成。在这里，我们表明Npnt表达与这一过程相关。吗啉代介导的Npnt敲低阻止了适当的瓣叶形成和小梁形成，并导致受精后7天的死亡率大于85%。最早观察到的表型是AV边界处的延伸管状结构。此外，参与心脏瓣膜形成的心肌基因（cspg 2、fibulin 1、tbx 2b、bmp 4）的表达扩大，并且沿着延伸的管状结构的内皮细胞表现出AV细胞的特征（has2、notch1b和Alcam表达，立方细胞形状）。抑制npnt吗啡类药物中的has2可以挽救内皮细胞的扩张，但不能挽救心肌的扩张。相比之下，减少BMP信号在npnt变形减少异位表达的心肌和内皮AV标志物。总之，我们的研究结果确定Npnt作为一种新的上游调节Bmp4-Has2信号，在AV管分化中起着至关重要的作用。
The extracellular matrix is crucial for organogenesis. It is a complex and dynamic component that regulates cell behavior by modulating the activity, bioavailability and presentation of growth factors to cell surface receptors. Here, we determined the role of the extracellular matrix protein Nephronectin (Npnt) in heart development using the zebrafish model system. The vertebrate heart is formed as a linear tube in which myocardium and endocardium are separated by a layer of extracellular matrix termed the cardiac jelly. During heart development, the cardiac jelly swells at the atrioventricular (AV) canal, which precedes valve formation. Here, we show that Npnt expression correlates with this process. Morpholino-mediated knockdown of Npnt prevents proper valve leaflet formation and trabeculation and results in greater than 85% lethality at 7 days post-fertilization. The earliest observed phenotype is an extended tube-like structure at the AV boundary. In addition, the expression of myocardial genes involved in cardiac valve formation (cspg2, fibulin 1, tbx2b, bmp4) is expanded and endocardial cells along the extended tube-like structure exhibit characteristics of AV cells (has2, notch1b and Alcam expression, cuboidal cell shape). Inhibition of has2 in npnt morphants rescues the endocardial, but not the myocardial, expansion. By contrast, reduction of BMP signaling in npnt morphants reduces the ectopic expression of myocardial and endocardial AV markers. Taken together, our results identify Npnt as a novel upstream regulator of Bmp4-Has2 signaling that plays a crucial role in AV canal differentiation.
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影响因子：
64.5
作者：
Fujiwara H;Ferreira M;Donati G;Marciano DK;Linton JM;Sato Y;Hartner A;Sekiguchi K;Reichardt LF;Watt FM
通讯作者：
Watt FM
影响因子：
2.7
作者：
Dorsky, RI;Sheldahl, LC;Moon, RT
通讯作者：
Moon, RT
DOI：
10.1073/pnas.042390499
发表时间：
2002-03-05
影响因子：
11.1
作者：
Gaussin, V;Van de Putte, T;Schneider, MD
通讯作者：
Schneider, MD
影响因子：
3.5
作者：
Fang, Ling;Kahai, Shireen;Yang, Burton B.
通讯作者：
Yang, Burton B.
影响因子：
4.8
作者：
Sato, Yuya;Uemura, Toshihiko;Sekiguchi, Kiyotoshi
通讯作者：
Sekiguchi, Kiyotoshi