Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv 69978, Israel.
Gen Comp Endocrinol. 2010 Jan 15;165(2):262-8. doi: 10.1016/j.ygcen.2009.07.001. Epub 2009 Jul 10.
Hypothalamic gonadotropin-releasing hormone (GnRH) neurons control pituitary gonadotropin secretion and gametogenesis. In the course of development, these neurons migrate from the olfactory placode to the hypothalamus. The precise molecular mechanism of this neuronal migration is unclear. Here, we investigated whether the chemokine receptor, Cxcr4b, and its cognate ligand, Cxcl12a, are required for proper migration of GnRH3 neurons in zebrafish. Deviated GnRH3 axonal projections and neuronal migration were detected in larvae that carry a homozygote cxcr4b mutation. Similarly, knockdown of Cxcr4b or Cxcl12a led to the appearance of abnormal GnRH3 axonal projections and cell migration, including absence of the characteristic lateral crossing of GnRH3 axons at the anterior commissure and optic chiasm. Double-labeling analysis has shown that cxcr4b and cxcl12a are expressed along the GnRH3 migration pathway (i.e. olfactory placode, terminal nerve and the optic chiasm). The results of this study suggest that the Cxcl12a-Cxcr4b ligand-receptor pair are involved in the migration of GnRH3 neurons in zebrafish, and are therefore crucial for the development of this system.
下丘脑促性腺激素释放激素（GnRH）神经元控制垂体促性腺激素的分泌和配子发生。在发育过程中，这些神经元从嗅基板迁移到下丘脑。这种神经元迁移的精确分子机制尚不清楚。在这里，我们研究了趋化因子受体 Cxcr4b 及其同源配体 Cxcl12a 是否需要 GnRH3 神经元在斑马鱼中的正确迁移。携带 cxcr4b 纯合突变的幼虫中检测到 GnRH3 轴突投射和神经元迁移的偏差。同样，Cxcr4b 或 Cxcl12a 的敲低导致 GnRH3 轴突投射和细胞迁移出现异常，包括 GnRH3 轴突在前连合和视神经交叉处的特征性侧向交叉缺失。双标记分析表明，cxcr4b 和 cxcl12a 沿 GnRH3 迁移途径（即嗅基板、终丝和视神经交叉）表达。这项研究的结果表明，Cxcl12a-Cxcr4b 配体-受体对参与了 GnRH3 神经元在斑马鱼中的迁移，因此对该系统的发育至关重要。
