VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels.
VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels.
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DOI：
10.1242/dev.063362
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Ruhrberg C
中科院分区：
文献类型：
--
作者：
Cariboni A;Davidson K;Dozio E;Memi F;Schwarz Q;Stossi F;Parnavelas JG;Ruhrberg C
促性腺激素释放激素（GnRH）神经元是神经内分泌细胞，在胚胎发育期间出生于鼻基板，并通过鼻和前脑迁移到下丘脑，在那里它们调节生殖。已经确定了许多引导其迁移的分子途径，但对控制迁移的GnRH神经元在不同环境中存活的因素知之甚少。我们以前报道过，3类信号蛋白SEMA3A通过其神经纤毛蛋白受体NRP1和NRP2发出信号，以组织轴突，引导迁移的GnRH神经元从其出生地进入大脑。通过结合基因改变的小鼠与体外模型的分析，我们在这里表明，替代neuropilin配体VEGF 164促进迁移GnRH神经元的存活，通过NRP1共激活ERK和AKT信号通路。我们还表明，生存信号依赖于神经元，而不是内皮细胞，NRP1的表达，它发生独立的KDR，血管中的主要VEGF受体。因此，VEGF164直接向发育中的GnRH神经元提供存活信号，而与其在血管中的作用无关。最后，我们表明，VEGF164介导的神经元存活和SEMA3A介导的轴突指导合作，以确保迁移的GnRH神经元到达大脑。因此，两种神经纤毛蛋白配体的缺失导致GnRH神经元系统的建立几乎完全失败。
Gonadotropin-releasing hormone (GnRH) neurons are neuroendocrine cells that are born in the nasal placode during embryonic development and migrate through the nose and forebrain to the hypothalamus, where they regulate reproduction. Many molecular pathways that guide their migration have been identified, but little is known about the factors that control the survival of the migrating GnRH neurons as they negotiate different environments. We previously reported that the class 3 semaphorin SEMA3A signals through its neuropilin receptors, NRP1 and NRP2, to organise the axons that guide migrating GnRH neurons from their birthplace into the brain. By combining analysis of genetically altered mice with in vitro models, we show here that the alternative neuropilin ligand VEGF164 promotes the survival of migrating GnRH neurons by co-activating the ERK and AKT signalling pathways through NRP1. We also demonstrate that survival signalling relies on neuronal, but not endothelial, NRP1 expression and that it occurs independently of KDR, the main VEGF receptor in blood vessels. Therefore, VEGF164 provides survival signals directly to developing GnRH neurons, independently of its role in blood vessels. Finally, we show that the VEGF164-mediated neuronal survival and SEMA3A-mediated axon guidance cooperate to ensure that migrating GnRH neurons reach the brain. Thus, the loss of both neuropilin ligands leads to an almost complete failure to establish the GnRH neuron system.
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影响因子：
7.8
作者：
Giacobini, Paolo;Messina, Andrea;Morello, Francesca;Ferraris, Nicoletta;Corso, Simona;Penachioni, Junia;Giordano, Silvia;Tamagnone, Luca;Fasolo, Aldo
通讯作者：
Fasolo, Aldo
影响因子：
3.3
作者：
Jin, K;Mao, XO;Greenberg, DA
通讯作者：
Greenberg, DA
DOI：
10.1073/pnas.97.18.10242
发表时间：
2000-08-29
影响因子：
11.1
作者：
Jin, KL;Mao, XO;Greenberg, DA
通讯作者：
Greenberg, DA
影响因子：
3.5
作者：
Cariboni, Anna;Davidson, Kathryn;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana
影响因子：
20.3
作者：
Fantin, Alessandro;Vieira, Joaquim M.;Ruhrberg, Christiana
通讯作者：
Ruhrberg, Christiana