Soluble factors guide gonadotropin-releasing hormone axonal targeting to the median eminence
Soluble factors guide gonadotropin-releasing hormone axonal targeting to the median eminence
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DOI：
10.1210/en.141.9.3065
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发表时间：
2000-09-01
期刊：
影响因子：
4.8
通讯作者：
Dobrjansky, A
中科院分区：
文献类型：
--
作者：
Gibson, MJ;Ingraham, L;Dobrjansky, A
GnRH神经元的轴突在发育早期终止于大脑内侧基底下丘脑（MBH）的正中隆起。同样，GnRH神经元移植的视前区（POA）组织内的第三脑室性腺功能减退的小鼠优先支配正中隆起。POA外植体与其他神经组织的器官型共培养表明，来自MBH的可溶性物质可能指导这种靶向。为了开始鉴定可扩散的化学引诱物，我们使用预孵育的肝素包被的丙烯酸珠来将特异性溶质呈现给插入室中的胶原蛋白和层粘连蛋白包被的膜上的POA外植体。与离珠侧相比，离珠侧生长的GnRH轴突数量多且长（P < 0.01）。相反，GnRH轴突没有表现出优先生长时，与浸泡在控制，确定的培养基珠孵育。MBH条件培养基的吸引力并不能推广到所有的神经内分泌神经元，因为它是没有看到甘丙肽免疫反应产物从POA外植体。小鼠脑微血管内皮细胞条件培养液中GnRH轴突也较多，但轴突长度无差异。碱性成纤维细胞生长因子（bFGF），内皮细胞和心室伸长细胞的成分，显着吸引更多和更长的GnRH轴突。因此，bFGF可能是介导GnRH向正中隆起生长的可溶性因子之一。然而，与生殖系统中的许多其他冗余一样，它不太可能是唯一的靶向因子，因为据报道bFGF敲除小鼠具有生殖能力。
Axons of GnRH neurons terminate at the median eminence in the medial basal hypothalamus (MBH) of the brain early in development. Similarly, GnRH neurons in grafts of preoptic area (POA) tissue within the third ventricle of hypogonadal mice preferentially innervate the median eminence. Organotypic cocultures of POA explants with other neural tissues suggest that a soluble substance(s) derived from the MBH may be directing this targeting. To begin to identify diffusable chemoattractants, we used preincubated heparin-coated acrylic beads to present specific solutes to POA explants on collagen- and laminin-coated membranes in insert chambers. GnRH axons grew on the membrane in greater number and with longer axons toward conditioned medium from MBH cultures than on the side away from the beads (P < 0.01). In contrast, GnRH axons showed no preferential outgrowth when incubated with beads soaked in control, defined medium. The attraction of MBH-conditioned medium was not generalizable to all neuroendocrine neurons, as it was not seen for galanin immunoreactive outgrowth from POA explants. There also were more GnRH axons toward conditioned medium from mouse brain microvascular endothelial cells, but no difference in axon length. Basic fibroblast growth factor (bFGF), a component of both endothelial cells and ventricular tanycytes, significantly attracted more and longer GnRH axons. Thus, bFGF may be one of the soluble factors directing GnRH outgrowth to the median eminence. However, as with so many other redundancies in the reproductive system, it is unlikely that it is the only targeting factor, as bFGF knockout mice are reported to be reproductively competent.