The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival
The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival
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DOI：
10.1242/dev.00640
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发表时间：
2003-09-01
期刊：
影响因子：
4.6
通讯作者：
Lehmann, R
中科院分区：
文献类型：
--
作者：
Molyneaux, KA;Zinszner, H;Lehmann, R
在小鼠胚胎中，生殖细胞在原肠胚形成过程中产生并迁移到早期性腺。首先，它们从原始条纹进入形成后肠的内胚层区域。在发育后期，第二阶段的迁移发生了，它们从肠道迁移到生殖器脊。在那里，它们与体细胞结合形成性腺。小鼠的体外研究和其他生物体的遗传研究表明，这个过程至少有一部分是对来自其他组织的分泌信号的反应。最近斑马鱼的遗传证据表明，基质细胞衍生因子1 （SDF1）及其g蛋白偶联受体CXCR4之间的相互作用，已经知道控制许多类型的正常和病理细胞迁移，也是原始生殖细胞正常迁移所必需的。我们发现，在小鼠中，生殖细胞的迁移和存活需要SDF1/CXCR4的相互作用。首先，迁移生殖细胞表达CXCR4，而体壁间质和生殖嵴表达配体SDF1。其次，在活胚胎培养物中添加外源性SDF1会导致生殖细胞从肠道异常迁移。第三，携带CXCR4靶向突变的胚胎中的生殖细胞不能正常定植性腺。然而，在后肠的早期阶段，生殖细胞在CXCR4（-/-）胚胎中不受影响。不同阶段的生殖细胞计数表明，SDF1/CXCR4相互作用也介导生殖细胞存活。这些结果表明，SDF1/CXCR4相互作用是原始生殖细胞对性腺定植的特异性需要，而不是生殖细胞迁移的早期阶段。这表明了部分机制具有高度的进化保守性，但也存在进化分歧。
In mouse embryos, germ cells arise during gastrulation and migrate to the early gonad. First, they emerge from the primitive streak into the region of the endoderm that forms the hindgut. Later in development, a second phase of migration takes place in which they migrate out of the gut to the genital ridges. There, they co-assemble with somatic cells to form the gonad. In vitro studies in the mouse, and genetic studies in other organisms, suggest that at least part of this process is in response to secreted signals from other tissues. Recent genetic evidence in zebrafish has shown that the interaction between stromal cell-derived factor 1 (SDF1) and its G-protein-coupled receptor CXCR4, already known to control many types of normal and pathological cell migrations, is also required for the normal migration of primordial germ cells. We show that in the mouse, germ cell migration and survival requires the SDF1/CXCR4 interaction. First, migrating germ cells express CXCR4, whilst the body wall mesenchyme and genital ridges express the ligand SDF1. Second, the addition of exogenous SDF1 to living embryo cultures causes aberrant germ cell migration from the gut. Third, germ cells in embryos carrying targeted mutations in CXCR4 do not colonize the gonad normally. However, at earlier stages in the hindgut, germ cells are unaffected in CXCR4(-/-) embryos. Germ cell counts at different stages suggest that SDF1/CXCR4 interaction also mediates germ cell survival. These results show that the SDF1/CXCR4 interaction is specifically required for the colonization of the gonads by primordial germ cells, but not for earlier stages in germ cell migration. This demonstrates a high degree of evolutionary conservation of part of the mechanism, but also an area of evolutionary divergence.