The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors
The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors
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DOI：
10.1523/jneurosci.4631-04.2005
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发表时间：
2005-04-20
影响因子：
5.3
通讯作者：
Miller, RJ
中科院分区：
文献类型：
--
作者：
Belmadani, A;Tran, PB;Miller, RJ
趋化因子及其受体对于造血/淋巴系统的发育和组织是必不可少的，并且现在已经显示由神经系统中的不同类型的细胞表达。在小鼠胚胎中，我们观察到表达趋化因子（CXC基序）受体4（CXCR 4）的神经嵴细胞迁移的背神经管和背根神经节（DRG）。基质细胞衍生因子-1（SDF-1）是CXCR 4的独特激动剂，其表达沿着嵴细胞至DRG的路径，表明SDF-1/CXCR 4信号传导是嵴细胞迁移所必需的。CXCR 4缺失小鼠表现出小且畸形的DRG。表达酪氨酸受体激酶A（TrkA）和TrkC（DRG感觉神经元发育所需的神经营养因子受体）的异位细胞表明向DRG的延迟迁移。在体外，CXCR 4趋化因子受体上调迁移祖细胞，因为他们退出小鼠神经管外植体，和SDF-1作为这些细胞的化学引诱剂。大多数表达CXCR 4的祖细胞分化形成具有多模态伤害感受器特性的感觉神经元。此外，DRG包含一群祖细胞，其在体外表达CXCR 4受体并分化为具有相似表型的神经元。我们的研究结果表明，SDF-1/CXCR 4信号传导在指导感觉神经元祖细胞迁移到DRG中以及在DRG合并后可能在发育的其他方面发挥重要作用。
Chemokines and their receptors are essential for the development and organization of the hematopoietic/lymphopoietic system and have now been shown to be expressed by different types of cells in the nervous system. In mouse embryos, we observed expression of the chemokine (CXC motif) receptor 4 (CXCR4) by neural crest cells migrating from the dorsal neural tube and in the dorsal root ganglia ( DRGs). Stromal cell-derived factor-1 (SDF-1), the unique agonist for CXCR4, was expressed along the path taken by crest cells to the DRGs, suggesting that SDF-1/CXCR4 signaling is needed for their migration. CXCR4 null mice exhibited small and malformed DRGs. Delayed migration to the DRGs was suggested by ectopic cells expressing tyrosine receptor kinase A ( TrkA) and TrkC, neurotrophin receptors required by DRG sensory neuron development. In vitro, the CXCR4 chemokine receptor was upregulated by migratory progenitor cells just as they exited mouse neural tube explants, and SDF-1 acted as a chemoattractant for these cells. Most CXCR4-expressing progenitors differentiated to form sensory neurons with the properties of polymodal nociceptors. Furthermore, DRGs contained a population of progenitor cells that expressed CXCR4 receptors in vitro and differentiated into neurons with a similar phenotype. Our findings indicate an important role for SDF-1/CXCR4 signaling in directing the migration of sensory neuron progenitors to the DRG and potentially in other aspects of development once the DRGs have coalesced.