University of Milan, Department of Pharmacological and Biomolecular Sciences, Via G. Balzaretti 9, 20133 Milan, Italy.
UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
Development. 2019 Nov 5;146(21):dev176461. doi: 10.1242/dev.176461.
Gonadotropin-releasing hormone (GnRH) neurons regulate puberty onset and sexual reproduction by secreting GnRH to activate and maintain the hypothalamic-pituitary-gonadal axis. During embryonic development, GnRH neurons migrate along olfactory and vomeronasal axons through the nose into the brain, where they project to the median eminence to release GnRH. The secreted glycoprotein SEMA3A binds its receptors neuropilin (NRP) 1 or NRP2 to position these axons for correct GnRH neuron migration, with an additional role for the NRP co-receptor PLXNA1. Accordingly, mutations in , , and have been linked to defective GnRH neuron development in mice and inherited GnRH deficiency in humans. Here, we show that only the combined loss of PLXNA1 and PLXNA3 phenocopied the full spectrum of nasal axon and GnRH neuron defects of SEMA3A knockout mice. Together with , the human orthologue of should therefore be investigated as a candidate gene for inherited GnRH deficiency.
促性腺激素释放激素（GnRH）神经元通过分泌 GnRH 来激活和维持下丘脑-垂体-性腺轴，从而调节青春期的开始和生殖。在胚胎发育过程中，GnRH 神经元通过鼻腔沿着嗅觉和犁鼻神经轴迁移到大脑中，在那里它们投射到正中隆起以释放 GnRH。分泌的糖蛋白 SEMA3A 与其受体神经纤毛蛋白（NRP）1 或 NRP2 结合，为这些轴突的正确 GnRH 神经元迁移定位，NRP 共受体 PLXNA1 发挥额外作用。因此， 、 、 和 中的突变已被链接到小鼠中 GnRH 神经元发育缺陷和人类遗传性 GnRH 缺乏。在这里，我们表明只有 PLXNA1 和 PLXNA3 的联合缺失才能模拟 SEMA3A 敲除小鼠的全部鼻轴和 GnRH 神经元缺陷表型。因此，与人 的同源物应作为遗传性 GnRH 缺乏的候选基因进行研究。
