miles-apart-Mediated regulation of cell-fibronectin interaction and myocardial migration in zebrafish.
miles-apart-Mediated regulation of cell-fibronectin interaction and myocardial migration in zebrafish.
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DOI：
10.1038/ncpcardio0764
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发表时间：
2007-02-01
影响因子：
--
通讯作者：
Izpisua Belmonte, Juan Carlos
中科院分区：
文献类型：
--
作者：
Matsui, Takaaki;Raya, Angel;Izpisua Belmonte, Juan Carlos
心肌前体细胞向胚胎中线的迁移是心管形成的基础，是心脏器官发生的关键过程。斑马鱼突变相隔数英里（mil），影响编码鞘氨醇-1-磷酸受体的基因，其特征是心肌前体细胞迁移缺陷，导致形成两个横向定位的心脏，这种情况称为心裂。在mil突变体中破坏心肌迁移的机制仍不清楚。为了研究mil如何调节这一过程，我们分析了mil和其他心肌迁移介质之间的相互作用。我们发现，mil功能与其他已知的心裂基因座，nat/纤连蛋白（nat/fn），它编码纤连蛋白，细胞外基质的主要成分，在心肌迁移的控制。通过使用胚胎斑马鱼细胞的原代培养系统，我们还表明，从鞘氨醇-1-磷酸受体的信号调节细胞在斑马鱼纤连蛋白的相互作用。此外，局部抑制和激活的细胞-纤连蛋白的相互作用，在心肌迁移的各个阶段揭示了细胞-纤连蛋白的相互作用的时间调节mil所需的适当的心肌迁移。我们的研究揭示了在斑马鱼心脏器官发生过程中，鞘氨醇-1-磷酸受体信号传导和细胞-纤连蛋白相互作用在心肌迁移控制中的新功能联系。
The migration of myocardial precursor cells towards the embryonic midline underlies the formation of the heart tube and is a key process of heart organogenesis. The zebrafish mutation miles-apart (mil), which affects the gene encoding a sphingosine-1-phosphate receptor, is characterized by defective migration of myocardial precursor cells and results in the formation of two laterally positioned hearts, a condition known as cardia bifida. The mechanism that disrupts myocardial migration in mil mutants remains largely unclear. To investigate how mil regulates this process, here we analyze the interactions between mil and other mediators of myocardial migration. We show that mil function is associated with the other known cardia bifida locus, natter/fibronectin (nat/fn), which encodes fibronectin, a major component of the extracellular matrix, in the control of myocardial migration. By using a primary culture system of embryonic zebrafish cells, we also show that signaling from the sphingosine-1-phosphate receptor regulates cell-fibronectin interactions in zebrafish. In addition, localized inhibition and activation of cell-fibronectin interactions during the stages of myocardial migration reveal that the temporal regulation of cell-fibronectin interaction by mil is required for proper myocardial migration. Our study reveals novel functional links between sphingosine-1-phosphate receptor signaling and cell-fibronectin interaction in the control of myocardial migration during zebrafish heart organogenesis.