Suppr超能文献

照亮终神经:揭示促性腺激素释放激素-1与嗅觉发育之间的联系。

Illuminating the Terminal Nerve: Uncovering the Link between GnRH-1 and Olfactory Development.

作者信息

Amato Enrico, Taroc Ed Zandro M, Forni Paolo E

出版信息

bioRxiv. 2023 Sep 3:2023.08.31.555770. doi: 10.1101/2023.08.31.555770.

Abstract

UNLABELLED

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 olfactory placode induce olfactory bulb morphogenesis. In mice, GnRH-1 neurons appear in the olfactory system around mid-gestation and migrate via the terminal nerve axons to different brain regions. The GnRH-1 neurons are crucial in controlling the hypothalamic-pituitary-gonadal (HPG) axis. Kallmann syndrome is characterized by impaired olfactory system development, defective olfactory bulbs, defective 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 olfactory bulb morphogenesis and GnRH-1 neuronal migration. loss-of-function mutations can cause Kallmann syndrome, 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 olfactory bulb morphogenesis. Single-cell RNA sequencing identified that the TN is formed by neurons that are 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.

KEY POINTS

  1. Pioneer or terminal nerve neurons play a crucial role in initiating the development of the olfactory bulbs. We found that the Prokineticin Receptor-2 gene, associated with Kallmann syndrome, is expressed by the olfactory pioneer/terminal nerve neurons.2) We genetically traced, isolated, and conducted Single-cell RNA sequencing on terminal nerve neurons of rodents. This analysis revealed a significant enrichment of gene expression related to Kallmann syndrome.3) Our study indicates that the investigation of Pioneer/terminal nerve neurons should be a pivotal focal point for comprehending developmental defects affecting olfactory and GnRH-1 systems.
摘要

未标记

在胚胎发育过程中,嗅基板(OP)产生迁移神经元,包括嗅觉先驱神经元、终神经(TN)细胞、促性腺激素释放激素-1(GnRH-1)神经元以及其他未明确特征的神经元。来自嗅基板的先驱神经元诱导嗅球形态发生。在小鼠中,GnRH-1神经元在妊娠中期左右出现在嗅觉系统中,并通过终神经轴突迁移到不同的脑区。GnRH-1神经元在控制下丘脑-垂体-性腺(HPG)轴方面至关重要。卡尔曼综合征的特征是嗅觉系统发育受损、嗅球缺陷、GnRH-1分泌缺陷和不育。嗅觉系统与GnRH-1发育之间的确切机制联系仍不清楚。对人类和小鼠的研究强调了促动力蛋白-2/促动力蛋白受体-2(Prokr2)信号通路在嗅球形态发生和GnRH-1神经元迁移中的重要性。功能丧失突变可导致卡尔曼综合征,因此Prokr2信号通路代表了一个独特的模型来解读嗅觉/GnRH-1联系。我们发现Prokr2在GnRH-1神经元形成、迁移和诱导嗅球形态发生的关键时期在TN神经元中表达。单细胞RNA测序确定TN由与嗅觉神经元不同的神经元组成。TN神经元表达多个与卡尔曼综合征相关的基因。我们的研究表明,先驱/TN神经元的异常发育可能导致卡尔曼综合征谱系。

关键点

1)先驱或终神经神经元在启动嗅球发育中起关键作用。我们发现与卡尔曼综合征相关的促动力蛋白受体-2基因由嗅觉先驱/终神经神经元表达。2)我们对啮齿动物的终神经神经元进行了基因追踪、分离和单细胞RNA测序。该分析揭示了与卡尔曼综合征相关的基因表达显著富集。3)我们的研究表明,对先驱/终神经神经元的研究应该是理解影响嗅觉和GnRH-1系统的发育缺陷的关键焦点。

相似文献

1
Illuminating the Terminal Nerve: Uncovering the Link between GnRH-1 and Olfactory Development.
bioRxiv. 2023 Sep 3:2023.08.31.555770. doi: 10.1101/2023.08.31.555770.
5
Nasal Placode Development, GnRH Neuronal Migration and Kallmann Syndrome.
Front Cell Dev Biol. 2019 Jul 11;7:121. doi: 10.3389/fcell.2019.00121. eCollection 2019.
6
Gli3 Regulates Vomeronasal Neurogenesis, Olfactory Ensheathing Cell Formation, and GnRH-1 Neuronal Migration.
J Neurosci. 2020 Jan 8;40(2):311-326. doi: 10.1523/JNEUROSCI.1977-19.2019. Epub 2019 Nov 25.
7
GPR37 Signaling Modulates Migration of Olfactory Ensheathing Cells and Gonadotropin Releasing Hormone Cells in Mice.
Front Cell Neurosci. 2019 May 9;13:200. doi: 10.3389/fncel.2019.00200. eCollection 2019.
8
Sexually dimorphic distribution of Prokr2 neurons revealed by the Prokr2-Cre mouse model.
Brain Struct Funct. 2017 Dec;222(9):4111-4129. doi: 10.1007/s00429-017-1456-5. Epub 2017 Jun 14.
9
Migration of GnRH-immunoreactive neurons from the olfactory placode to the brain: a study using avian embryonic chimeras.
Brain Res Dev Brain Res. 1996 Sep 2;95(2):234-44. doi: 10.1016/0165-3806(96)00078-8.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验