Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1)
Impaired colonization of the gonads by primordial germ cells in mice lacking a chemokine, stromal cell-derived factor-1 (SDF-1)
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DOI：
10.1073/pnas.0730719100
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发表时间：
2003-04-29
影响因子：
11.1
通讯作者：
Nagasawa, T
中科院分区：
文献类型：
--
作者：
Ara, T;Nakamura, Y;Nagasawa, T
原始生殖细胞 (PGC) 是精子或卵母细胞的创始人。 PGC 在发育过程中通过胚胎组织迁移并定植于性腺。然而，PGC 在哺乳动物性腺中定植所必需的细胞因子仍不清楚。基质细胞衍生因子 1（SDF-1，也称为 PBSF 和 CXCL12）是趋化因子的成员，趋化因子是结构相关的趋化细胞因子家族。 SDF-1 及其主要生理受体 CXCR4 在发育过程中具有多种重要功能，包括造血细胞在骨髓中的定植和胚胎发生期间小脑内神经元的定位以及 B 淋巴细胞生成和心血管发生。在这里，我们发现PGCs在细胞表面表达CXCR4，并且在SDF-1(-/-)小鼠中，PGCs通过胚胎组织进行定向迁移，但性腺中PGCs的数量显着减少。在突变小鼠中，性腺内 PGC 的增殖似乎正常。这些发现揭示了 SDF-1 在小鼠 PGC 发育中的重要作用，可能是通过控制 PGC 对性腺的定植来实现的。
Primordial germ cells (PGCs) are the founders of sperm or oocytes. PGCs migrate through the tissues of the embryos and colonize the gonads during development. However, the cytokines essential for colonization of the gonads by PGCs in mammals remain unclear. Stromal cell-derived factor-1 (SDF-1, also called PBSF and CXCL12) is a member of chemokines, a family of structurally related chemoattractive cytokines. SDF-1 and its primary physiologic receptor CXCR4 have multiple essential functions in development including colonization of bone marrow by hematopoietic cells and neuron localization within cerebellum during embryogenesis as well as B lymphopoiesis and cardiovasculogenesis. Here, we have shown that PGCs have cell-surface expression of CXCR4 and that, in SDF-1(-/-) mice, PGCs undergo directed migration through tissues of embryos, but the numbers of PGCs in the gonads are significantly reduced. The proliferation of PGCs within the gonads seems normal in the mutant mice. These findings reveal the essential role for SDF-1 in murine PGC development likely by controlling colonization of the gonads by PGCs.