Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling.
Specification of GnRH-1 neurons by antagonistic FGF and retinoic acid signaling.
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DOI：
10.1016/j.ydbio.2011.12.016
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发表时间：
2012-02-15
影响因子：
2.7
通讯作者：
Streit A
中科院分区：
文献类型：
--
作者：
Sabado V;Barraud P;Baker CV;Streit A
下丘脑吻端和基底前脑中的一小部分神经内分泌细胞是脊椎动物生殖的关键调节器。它们分泌促性腺激素释放激素（GnRH-1），与大脑的许多区域交流，并整合多种输入来控制性腺成熟，青春期和性行为。在人类中，GnRH-1系统的破坏导致低促性腺激素性腺症和卡尔曼综合征。与中枢神经系统中的其他神经元不同，GnRH-1神经元产生于外周，然而它们的胚胎起源是有争议的，并且控制其初始特化的分子机制尚不清楚。在这里，我们提供的证据表明，在小鸡GnRH-1神经元起源于嗅基板，在那里他们被指定后不久，嗅觉感觉神经元。FGF信号是必需的，足以诱导GnRH-1神经元，而视黄酸抑制它们的形成。这两种途径相互调节和拮抗，我们的研究结果表明，信号传导的时间是正常的GnRH-1神经元形成的关键。虽然Kallmann综合征通常归因于FGF信号传导受损导致的GnRH-1神经元迁移失败，但我们的研究结果表明，至少在某些Kallmann患者中，这些神经元可能从未被指定。此外，这项研究强调了GnRH-1神经元与其靶点和调节剂之间的密切胚胎关系。
A small population of neuroendocrine cells in the rostral hypothalamus and basal forebrain is the key regulator of vertebrate reproduction. They secrete gonadotropin-releasing hormone (GnRH-1), communicate with many areas of the brain and integrate multiple inputs to control gonad maturation, puberty and sexual behavior. In humans, disruption of the GnRH-1 system leads to hypogonadotropic gonadism and Kallmann syndrome. Unlike other neurons in the central nervous system, GnRH-1 neurons arise in the periphery, however their embryonic origin is controversial, and the molecular mechanisms that control their initial specification are not clear. Here, we provide evidence that in chick GnRH-1 neurons originate in the olfactory placode, where they are specified shortly after olfactory sensory neurons. FGF signaling is required and sufficient to induce GnRH-1 neurons, while retinoic acid represses their formation. Both pathways regulate and antagonize each other and our results suggest that the timing of signaling is critical for normal GnRH-1 neuron formation. While Kallmann’s syndrome has generally been attributed to a failure of GnRH-1 neuron migration due to impaired FGF signaling, our findings suggest that in at least some Kallmann patients these neurons may never be specified. In addition, this study highlights the intimate embryonic relationship between GnRH-1 neurons and their targets and modulators in the adult.