Development And Regulation Of The Luteinizing Hormone Re

对生殖至关重要的LHRH神经元来自鼻侧胎盘，并迁移到大脑中，在那里它们成为下丘脑-垂体-性腺轴的组成部分。我们在正常/转基因动物和鼻腔外植体中研究了促性腺激素释放激素神经元分化、迁移和轴突定位的机制(S)。利用鼻腔外植体、细胞系、正常动物和转基因动物，研究了LHRH神经元对LHRH基因表达、多肽合成和分泌的内在和跨突触调节。我们实验室以前的工作1)表明嗅轴突的生长和LHRH神经元的迁移发生在分离的嗅窝组织中，2)揭示了嗅轴突的指导线索‘定位于中线鼻软骨组织，3)表明GABA在鼻区LHRH神经元的迁移中是一个重要因素，4)发现了一个名为NELF的新基因，我们假设它通过同源相互作用影响LHRH神经元在嗅轴突上的迁移。在过去的一年里，我们继续研究NELF在发育过程中的表达模式。NELF主要局限于三叉神经核和中枢神经系统组织，在出生前和出生后高表达于丘脑。此外，我们还发现，鼻腔外植体中LHRH神经元的成熟与体内LHRH神经元在肽的合成和加工方面是平行的，并且在缺乏中枢神经系统组织的情况下，LHRH神经元表现出同步的神经元活动。未来的研究方向是对嗅觉和LHRH神经元系统的发育至关重要的分子和信号，以及调节LHRH神经元活动的机制。正在进行的具体研究集中在：1)分离影响嗅轴突生长的中线线索；2)NELF和其他分子在LHRH迁移中的作用；3)识别LHRH神经元中参与节律活动建立/维持的起搏分子；4)作为GABA能刺激的基因在LHRH神经元中的差异表达；以及5)LHRH神经元中受体和通道的表达作为发育的函数。

LHRH neurons, critical for reproduction, are derived from the nasal placode and migrate into the brain where they become integral members of the hypothalamic-pituitary-gonadal axis. We study mechanism(s) underlying LHRH neuronal differentiation, migration and axonal targeting in normal/transgenic animals, and nasal explants. Intrinsic and trans-synaptic regulation of LHRH gene expression, peptide synthesis and secretion in LHRH neurons are studied using nasal explants, cell lines and normal and transgenic animals. Previous work in our lab 1) showed that outgrowth of olfactory axons and migration of LHRH neurons occur in isolated olfactory pit tissue, 2) revealed olfactory axon 'guidance cues' localized to midline nasal cartilagenous tissue, 3) showed GABA was an important factor in the migration of LHRH neurons in nasal regions and 4) identified a novel gene termed NELF which we hypothesize acts via a homophilic interaction to influence LHRH neuronal migration on olfactory axons. Over the past year, we have continued our work characterizing the expression pattern of NELF during development. NELF is primarily limited to PNS and CNS tissues, being highly expressed in the thalamus both prenatally and postnatally. In addition, we have shown that maturation of LHRH neurons in nasal explants parallels LHRH neurons in vivo, with respect to peptide synthesis and processing and that devoid of CNS tissues LHRH neurons exhibit synchronous neuronal activity. Future studies are directed at the molecules and cues important for development of the olfactory and LHRH neuronal systems as well as the mechanisms regulating LHRH neuronal activity. Specific studies in progress focused on: 1) isolation of midline cues which influence olfactory axon outgrowth; 2) the role of NELF and other molecules in LHRH migration, 3) identifying pacemaker molecules in LHRH neurons that participate in establishment/maintenance of rhythmic activity 4) genes differentially expressed in LHRH neurons as a function of GABAergic stimulation and 5) expression of receptors and channels in LHRH neurons as a function of development.