Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4
Embryonic expression and function of the chemokine SDF-1 and its receptor, CXCR4
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DOI：
10.1006/dbio.1999.9405
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发表时间：
1999-09-15
影响因子：
2.7
通讯作者：
Palis, J
中科院分区：
文献类型：
--
作者：
McGrath, KE;Koniski, AD;Palis, J
定向细胞运动对于胚胎发生和造血作用都是不可或缺的。在成年个体中，分泌蛋白的趋化因子家族通过G蛋白偶联趋化因子受体发出造血细胞迁移的信号。我们通过使用简并引物在胚胎第7.5天（E7.5）进行逆转录聚合酶链反应，或者对E8.5和E12.5组织进行核糖核酸酶保护分析，检测到趋化因子受体信使核糖核酸在胚胎中的表达。在所有样本中，编码CXCR4的信使核糖核酸是检测到的主要趋化因子受体，特别是在早期（E7.5和E8.5）。其他趋化因子受体信使核糖核酸（CCR1、CCR4、CCR5、CCR2和CXCR2）在E12.5组织中被发现，其在时间和空间上与定型（成年样）造血作用一致。通过原位杂交将CXCR4的表达与其唯一已知的配体——基质细胞衍生因子 - 1（SDF - 1）的表达进行比较。在器官发生过程中，这些基因具有动态且互补的表达模式，特别是在发育中的神经、心脏、血管、造血和颅面系统中。在CXCR4和SDF - 1缺陷型小鼠中，已经报道了前四个系统存在缺陷。我们的研究为其中一些缺陷提出了新的潜在机制，以及超出已报道异常范围的其他作用。在发育早期，这些基因的表达与原肠胚形成过程中的迁移相关。迁移的细胞（中胚层和定型内胚层）含有CXCR4信使核糖核酸，而胚胎外胚层细胞表达SDF - 1。通过迁移实验证明了中胚层细胞以及E12.5造血祖细胞中SDF - 1的功能性信号传导。迁移在最佳剂量下发生，该剂量与在成年造血细胞中发现的相似，并且依赖于梯度中SDF - 1的存在。这项工作表明趋化因子信号传导在多种胚胎发生事件中起作用。（C）1999年学术出版社
Directed cell movement is integral to both embryogenesis and hematopoiesis. In the adult, the chemokine family of secreted proteins signals migration of hematopoietic cells through G-coupled chemokine receptors. We detected embryonic expression of chemokine receptor messages by RT-PCR with degenerate primers at embryonic day 7.5 (E7.5) or by RNase protection analyses of E8.5 and E12.5 tissues. In all samples, the message encoding CXCR4 was the predominate chemokine receptor detected, particularly at earlier times (E7.5 and E8.5). Other chemokine receptor messages (CCR1, CCR4, CCR5, CCR2, and CXCR2) were found in E12.5 tissues concordant temporally and spatially with definitive (adult-like) hematopoiesis. Expression of CXCR4 was compared with that of its only known ligand, stromal cell-derived factor-1 (SDF-1), by in situ hybridization. During organogenesis, these genes have dynamic and complementary expression patterns particularly in the developing neuronal, cardiac, vascular, hematopoietic, and craniofacial systems. Defects in the first four of these systems have been reported in CXCR4- and SDF-1-deficient mice. Our studies suggest new potential mechanisms for some of these defects as well as additional roles beyond the scope of the reported abnormalities. Earlier in development, expression of these genes correlates with migration during gastrulation. Migrating cells (mesoderm and definitive endoderm) contain CXCR4 message while embryonic ectoderm cells express SDF-1. Functional SDF-1 signaling in midgastrula cells as well as E12.5 hematopoietic progenitors was demonstrated by migration assays. Migration occurred with an optimum dose similar to that found for adult hematopoietic cells and was dependent on the presence of SDF-1 in a gradient. This work suggests roles for chemokine signaling in multiple embryogenic events. (C) 1999 Academic Press.