The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle in zebrafish.
The chemokine Sdf-1 and its receptor Cxcr4 are required for formation of muscle in zebrafish.
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DOI：
10.1186/1471-213x-7-54
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发表时间：
2007-05-22
影响因子：
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通讯作者：
Korzh, Vladimir
中科院分区：
文献类型：
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作者：
Chong, Shang-Wei;Nguyet, Le-Minh;Jiang, Yun-Jin;Korzh, Vladimir
在发育过程中，细胞迁移发生在许多细胞类型分化之前。趋化因子受体Cxcr4及其配体Sdf1与包括阑尾肌在内的多种细胞系的迁移有关。我们剖析了sdf1-cxcr4在骨骼肌发生中的作用。我们证明了受体cxcr4a在体细胞的中前部表达，这表明趋化因子信号在体细胞的这一区域起作用。以前的报道强调Sdf1a和Cxcr4b的合作。我们发现，在早期肌肉形成过程中，Sdf1a与斑马鱼的第二个Cxcr4 - Cxcr4a合作，导致成肌细胞承诺形成快速肌肉。破坏这种趋化因子信号导致myoD和myf5表达减少和快速纤维形成。此外，我们发现MyoD和Myf5的二聚化伙伴E12与Sonic hedgehog基因不同，可以正向调节cxcr4a和sdf1a的转录，通过诱导id2的表达抑制这些基因。我们揭示了cxcr4a-sdf1a与肌生成调节因子编码基因之间的调节反馈机制，该机制参与了快肌纤维的分化。这证明了趋化因子信号在骨骼肌发育过程中的作用。
During development cell migration takes place prior to differentiation of many cell types. The chemokine receptor Cxcr4 and its ligand Sdf1 are implicated in migration of several cell lineages, including appendicular muscles. We dissected the role of sdf1-cxcr4 during skeletal myogenesis. We demonstrated that the receptor cxcr4a is expressed in the medial-anterior part of somites, suggesting that chemokine signaling plays a role in this region of the somite. Previous reports emphasized co-operation of Sdf1a and Cxcr4b. We found that during early myogenesis Sdf1a co-operates with the second Cxcr4 of zebrafish – Cxcr4a resulting in the commitment of myoblast to form fast muscle. Disrupting this chemokine signal caused a reduction in myoD and myf5 expression and fast fiber formation. In addition, we showed that a dimerization partner of MyoD and Myf5, E12, positively regulates transcription of cxcr4a and sdf1a in contrast to that of Sonic hedgehog, which inhibited these genes through induction of expression of id2. We revealed a regulatory feedback mechanism between cxcr4a-sdf1a and genes encoding myogenic regulatory factors, which is involved in differentiation of fast myofibers. This demonstrated a role of chemokine signaling during development of skeletal muscles.