Migration of early olfactory neuronal progenitors

早期嗅觉神经元祖细胞的迁移

基本信息

批准号：
7467222
负责人：
GERALD A SCHWARTING
金额：
$ 29.67万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-09 至 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7467222
关键词：
AMD3100 Axon Biology Brain CXCR4 Receptors CXCR4 gene Cell Death Induction Chemotactic Factors Collaborations Competence Complex Condition Cues Destinations Development Diagnosis Embryo Ensure Equilibrium Failure Gene Mutation General Hospitals Generations Genes Gills Gonadotropin Hormone Releasing Hormone Gonadotropins Green Fluorescent Proteins Growth Human Hypothalamic structure Immigration In Vitro Individual KISS1R gene Kallmann Syndrome Klinefelter&apos s Syndrome Lead Left Massachusetts Mesenchyme Modeling Molecular Movement Mus Mutant Strains Mice Mutation Neurons Nose Numbers Organ Culture Techniques Pathway interactions Patients Play Positioning Attribute Property Prosencephalon Recombinants Role Signal Transduction Slice Stromal Cell-Derived Factor 1 System Testing Transgenic Animals Vertebrates Video Microscopy Vomeronasal Nerves basal forebrain base cell motility chemokine cribriform plate hypothalamic pituitary gonadal axis in vivo inhibitor/antagonist migration mouse model nerve stem cell olfactory bulb pituitary gonadal axis postnatal receptor reproductive research study selective expression vomeronasal organ

项目摘要

DESCRIPTION (provided by applicant): The secretion of Gonadotropin-releasing hormone (GnRH, also called LHRH) is critical for regulating the pituitary-gonadal axis and ensuring reproductive competence for virtually all vertebrates. GnRH neurons migrate from the olfactory placode across the cribriform plate and olfactory bulb, into the forebrain and hypothalamus during embryonic and early postnatal development. The migratory pathway for these neurons consists of axons that originate in the vomeronasal organ (VNO), and project beyond the olfactory bulb directly into the rostral forebrain. Preliminary studies show that SDF-1/CXCR4 signaling plays a critical role in GnRH neuron migration. Virtually no GnRH neurons reach the ventral forbrain in CXCR4-/- mice. These mice may represent an ideal model for Kallmann Syndrome (KS) or Idiopathic Hypogonadotropic Hypogonadism (IHH). We will analyze the role of SDF-1/CXCR4 in vivo and in vitro studies in mouse and will seek to determine whether individuals with KS or IHH may have SDF-1 or CXCR4 gene mutations. We will also analyze the role of kisspeptin/GPR54 signaling for their ability to influence the mobility and direction of movement of subsets of GnRH neurons. These experiments are proposed to balance studies in vivo using normal and mutant mice with studies in vitro that test particular pathways or mechanisms. The complementary approach is important for ensuring that our results will be relevant to the basic biology of the GnRH neuronal system. In vivo, we will use several lines of mutant mice to analyze their roles in migration of GnRH neurons. In vitro, we will test whether different cues signal through the same or similar mechanisms to drive GnRH neuron movement/migration. We will test mechanisms in individual GnRH neurons by video microscopy using in vitro slice cultures derived from transgenic animals in which green fluorescent protein (GFP) is selectively expressed in GnRH neurons. These studies will lead to an understanding of the complex factors that guide GnRH neurons to their proper destinations in the hypothalamus to control the hypothalamic-pituitary-gonadal axis.

描述（由申请人提供）：促性腺激素释放激素（GNRH，也称为LHRH）的分泌对于调节垂体 - 基达轴并确保几乎所有脊椎动物的生殖能力至关重要。 GnRH神经元从遍布片状板和嗅球的嗅觉片段迁移到胚胎和早期产后发育期间的前脑和下丘脑。这些神经元的迁移途径由起源于呕吐器器官（VNO）的轴突组成，并直接进入嗅球范围内的轴突直接进入前脑。初步研究表明，SDF-1/CXCR4信号在GNRH神经元迁移中起关键作用。几乎没有GnRH神经元在CXCR4 - / - 小鼠中到达腹侧脑。这些小鼠可能代表了Kallmann综合征（KS）或特发性性低肿瘤性性低肿瘤（IHH）的理想模型。我们将分析小鼠中SDF-1/CXCR4在体内和体外研究中的作用，并试图确定患有KS或IHH的个体是否具有SDF-1或CXCR4基因突变。我们还将分析Kisspeptin/gpr54信号传导的作用，以影响GNRH神经元子集运动的迁移率和方向。提出了这些实验，可以使用正常小鼠和突变小鼠与测试特定途径或机制的体外研究平衡体内研究。补充方法对于确保我们的结果与GNRH神经元系统的基本生物学相关至关重要。在体内，我们将使用几条突变小鼠分析它们在GnRH神经元迁移中的作用。在体外，我们将测试通过相同或相似的机制信号来驱动GNRH神经元运动/迁移。我们将使用视频显微镜在单个GNRH神经元中的体外切片培养物中测试机制，该体外切片培养物衍生自转基因动物，其中绿色荧光蛋白（GFP）在GNRH神经元中选择性地表达。这些研究将导致对引导GNRH神经元在下丘脑中适当目的地的复杂因素的理解，以控制下丘脑 - 垂体 - 辅助轴。