PDF(Pubmed)
Abstract：
During embryonic development, the olfactory placode (OP) generates migratory neurons, including olfactory pioneer neurons, cells of the terminal nerve (TN), gonadotropin-releasing hormone-1 (GnRH-1) neurons, and other uncharacterized neurons. Pioneer neurons from the OP induce olfactory bulb (OB) morphogenesis. In mice, GnRH-1 neurons appear in the olfactory system around mid-gestation and migrate via the TN axons to different brain regions. The GnRH-1 neurons are crucial in controlling the hypothalamic-pituitary-gonadal axis. Kallmann syndrome is characterized by impaired olfactory system development, defective OBs, secretion of GnRH-1, and infertility. The precise mechanistic link between the olfactory system and GnRH-1 development remains unclear. Studies in humans and mice highlight the importance of the prokineticin-2/prokineticin-receptor-2 (Prokr2) signaling pathway in OB morphogenesis and GnRH-1 neuronal migration. Prokr2 loss-of-function mutations can cause Kallmann syndrome (KS), and hence the Prokr2 signaling pathway represents a unique model to decipher the olfactory/GnRH-1 connection. We discovered that Prokr2 is expressed in the TN neurons during the critical period of GnRH-1 neuron formation, migration, and induction of OB morphogenesis. Single-cell RNA sequencing identified that the TN is formed by neurons distinct from the olfactory neurons. The TN neurons express multiple genes associated with KS. Our study suggests that the aberrant development of pioneer/TN neurons might cause the KS spectrum.
摘要：
在胚胎发育过程中,嗅觉电位（OP）产生迁移神经元，包括嗅觉先驱神经元，末梢神经细胞（TN），促性腺激素释放激素-1（GnRH-1）神经元，和其他未表征的神经元。来自OP的先锋神经元诱导嗅球（OB）形态发生。在老鼠身上,GnRH-1神经元出现在妊娠中期的嗅觉系统中，并通过TN轴突迁移到不同的大脑区域。GnRH-1神经元对控制下丘脑-垂体-性腺轴至关重要。Kallmann综合征的特征是嗅觉系统发育受损，有缺陷的OOB,分泌GnRH-1和不孕症。嗅觉系统与GnRH-1发育之间的精确机制联系尚不清楚。在人类和小鼠中的研究强调了前动力蛋白2/前动力蛋白受体2（Prokr2）信号通路在OB形态发生和GnRH-1神经元迁移中的重要性。Prokr2功能丧失突变可导致Kallmann综合征（KS），因此，Prokr2信号通路代表了破译嗅觉/GnRH-1连接的独特模型。我们发现Prokr2在GnRH-1神经元形成的关键时期在TN神经元中表达，迁移,和OB形态发生的诱导。单细胞RNA测序鉴定TN由不同于嗅觉神经元的神经元形成。TN神经元表达多个与KS相关的基因。我们的研究表明，先锋/TN神经元的异常发育可能导致KS谱。
