SDF and GABA interact to regulate axophilic migration of GnRH neurons
SDF and GABA interact to regulate axophilic migration of GnRH neurons
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DOI：
10.1242/jcs.101675
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发表时间：
2012-11-01
影响因子：
4
通讯作者：
Wray, Susan
中科院分区：
文献类型：
--
作者：
Casoni, Filippo;Hutchins, B. Ian;Wray, Susan
基质衍生生长因子（SDF-1）和γ-氨基丁酸（GABA）是两种细胞外因子，在发育过程中调节神经元迁移的速率，并可能协同作用。这种相互作用的分子机制尚不清楚。促性腺激素释放激素-1（GnRH）神经元是脊椎动物生殖所必需的。在发育过程中，这些神经元从鼻基板出现，并通过筛板迁移到大脑。SDF-1和GABA均已显示分别通过加速和减慢迁移来调节GnRH神经元迁移的速率。因此，该系统用于探索这些分子在发育期间产生协调细胞运动的机制。在本研究中，GABA和SDF-1显示通过激活去极化或超极化信号通路对细胞运动速度产生相反的影响，GABA通过氯的变化，SDF-1通过钾的变化。还发现GABA和SDF-1协同作用以促进线性运动而不是随机运动。因此，这些信号通路的同时激活导致细胞速度的严格控制和GnRH神经元迁移通路方向性的沿着改善。
Stromal derived growth factor (SDF-1) and gamma-aminobutyric acid (GABA) are two extracellular cues that regulate the rate of neuronal migration during development and may act synergistically. The molecular mechanisms of this interaction are still unclear. Gonadotropin releasing hormone-1 (GnRH) neurons are essential for vertebrate reproduction. During development, these neurons emerge from the nasal placode and migrate through the cribriform plate into the brain. Both SDF-1 and GABA have been shown to regulate the rate of GnRH neuronal migration by accelerating and slowing migration, respectively. As such, this system was used to explore the mechanism by which these molecules act to produce coordinated cell movement during development. In the present study, GABA and SDF-1 are shown to exert opposite effects on the speed of cell movement by activating depolarizing or hyperpolarizing signaling pathways, GABA via changes in chloride and SDF-1 via changes in potassium. GABA and SDF-1 were also found to act synergistically to promote linear rather than random movement. The simultaneous activation of these signaling pathways, therefore, results in tight control of cellular speed and improved directionality along the migratory pathway of GnRH neurons.