Chong Shang-Wei, Nguyet Le-Minh, Jiang Yun-Jin, Korzh Vladimir
Laboratory of Fish Developmental Biology, Institute of Molecular and Cell Biology, Proteos, Singapore.
BMC Dev Biol. 2007 May 22;7:54. doi: 10.1186/1471-213X-7-54.
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.
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与包括附肢肌肉在内的几种细胞谱系的迁移有关。
我们剖析了sdf1-cxcr4在骨骼肌生成过程中的作用。我们证明受体cxcr4a在体节的内侧前部表达，这表明趋化因子信号在体节的这个区域发挥作用。先前的报道强调了Sdf1a和Cxcr4b的协同作用。我们发现，在早期肌生成过程中，Sdf1a与斑马鱼的第二个Cxcr4——Cxcr4a协同作用，导致成肌细胞定向形成快肌。破坏这种趋化因子信号会导致myoD和myf5表达以及快肌纤维形成减少。此外，我们表明，与Sonic hedgehog相反，MyoD和Myf5的二聚化伙伴E12正向调节cxcr4a和sdf1a的转录，Sonic hedgehog通过诱导id2的表达来抑制这些基因。
我们揭示了cxcr4a-sdf1a与编码生肌调节因子的基因之间的调节反馈机制，该机制参与快肌纤维的分化。这证明了趋化因子信号在骨骼肌发育过程中的作用。
