Bagri Anil, Gurney Theresa, He Xiaoping, Zou Yong-Rui, Littman Dan R, Tessier-Lavigne Marc, Pleasure Samuel J
Neurodevelopmental Disorders Laboratory, Department of Neurology, Program in Neuroscience, University of California, San Francisco, CA 94143-0435, USA.
Development. 2002 Sep;129(18):4249-60. doi: 10.1242/dev.129.18.4249.
The dentate gyrus is the primary afferent pathway into the hippocampus, but there is little information concerning the molecular influences that govern its formation. In particular, the control of migration and cell positioning of dentate granule cells is not clear. We have characterized more fully the timing and route of granule cell migration during embryogenesis using in utero retroviral injections. Using this information, we developed an in vitro assay that faithfully recapitulates important events in dentate gyrus morphogenesis. In searching for candidate ligands that may regulate dentate granule cell migration, we found that SDF1, a chemokine that regulates cerebellar and leukocyte migration, and its receptor CXCR4 are expressed in patterns that suggest a role in dentate granule cell migration. Furthermore, CXCR4 mutant mice have a defect in granule cell position. Ectopic expression of SDF1 in our explant assay showed that it directly regulates dentate granule cell migration. Our study shows that a chemokine is necessary for the normal development of the dentate gyrus, a forebrain structure crucial for learning and memory.
齿状回是进入海马体的主要传入通路，但关于控制其形成的分子影响的信息却很少。特别是，齿状颗粒细胞的迁移和细胞定位的控制尚不清楚。我们通过子宫内逆转录病毒注射更全面地描述了胚胎发育过程中颗粒细胞迁移的时间和途径。利用这些信息，我们开发了一种体外试验，该试验忠实地再现了齿状回形态发生中的重要事件。在寻找可能调节齿状颗粒细胞迁移的候选配体时，我们发现SDF1（一种调节小脑和白细胞迁移的趋化因子）及其受体CXCR4的表达模式表明它们在齿状颗粒细胞迁移中发挥作用。此外，CXCR4突变小鼠在颗粒细胞定位上存在缺陷。在我们的外植体试验中，SDF1的异位表达表明它直接调节齿状颗粒细胞迁移。我们的研究表明，趋化因子对于齿状回的正常发育是必需的，齿状回是对学习和记忆至关重要的前脑结构。
