Control of cell migration in the development of the posterior lateral line: antagonistic interactions between the chemokine receptors CXCR4 and CXCR7/RDC1.
Control of cell migration in the development of the posterior lateral line: antagonistic interactions between the chemokine receptors CXCR4 and CXCR7/RDC1.
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DOI：
10.1186/1471-213x-7-23
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发表时间：
2007-03-29
影响因子：
--
通讯作者：
Ghysen A
中科院分区：
文献类型：
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作者：
Dambly-Chaudière C;Cubedo N;Ghysen A
硬骨鱼后侧线的形成依赖于原基的迁移，该原基起源于耳囊附近并向尾尖移动。原基后缘的细胞群有规律地间隔减速，最终停留下来分化为感觉器官。原基的迁移由趋化因子SDF1及其受体CXCR4驱动，它们分别由基因sdf1a和cxcr4b编码。cxcr4b在迁移细胞中表达，在原基的后缘细胞中下调。sdf1a在迁移路径上表达。然而，没有证据表明sdf1a表达存在梯度，并且迁移方向性的起源尚不清楚。
在此，我们记录了第二个趋化因子受体基因cxcr7在迁移原基中的表达。我们表明cxcr7在原基的后缘细胞中高度表达，而在前沿细胞中完全不表达，这种模式与cxcr4b的模式互补。尽管cxcr7不在引导原基迁移的细胞中表达，但其失活会导致迁移受损。然而，cxcr4b、cxcr7双吗啉代胚胎的表型表明，CXCR7对原基细胞的迁移能力没有贡献。我们还表明，在没有cxcr4b的情况下，cxcr7的表达在停滞的原基中变得普遍存在。
我们的观察结果表明，CXCR7是为迁移提供方向性所必需的。我们提出，一旦原基与SDF1条带接触，方向性就会施加于原基上，并且在整个迁移过程中通过这两种受体之间的负相互作用得以维持。
The formation of the posterior lateral line of teleosts depends on the migration of a primordium that originates near the otic vesicle and moves to the tip of the tail. Groups of cells at the trailing edge of the primordium slow down at regular intervals and eventually settle to differentiate as sense organs. The migration of the primordium is driven by the chemokine SDF1 and by its receptor CXCR4, encoded respectively by the genes sdf1a and cxcr4b. cxcr4b is expressed in the migrating cells and is down-regulated in the trailing cells of the primordium. sdf1a is expressed along the path of migration. There is no evidence for a gradient of sdf1a expression, however, and the origin of the directionality of migration is not known. Here we document the expression of a second chemokine receptor gene, cxcr7, in the migrating primordium. We show that cxcr7 is highly expressed in the trailing cells of the primordium but not at all in the leading cells, a pattern that is complementary to that of cxcr4b. Even though cxcr7 is not expressed in the cells that lead primordium migration, its inactivation results in impaired migration. The phenotypes of cxcr4b, cxcr7 double morphant embryos suggest, however, that CXCR7 does not contribute to the migratory capabilities of primordium cells. We also show that, in the absence of cxcr4b, expression of cxcr7 becomes ubiquitous in the stalled primordium. Our observations suggest that CXCR7 is required to provide directionality to the migration. We propose that directionality is imposed on the primordium as soon as it comes in contact with the stripe of SDF1, and is maintained throughout migration by a negative interaction between the two receptors.