FGF Regulation of GnRH Neurons

FGF 对 GnRH 神经元的调节

基本信息

批准号：
6747775
负责人：
Pei-San Tsai
金额：
$ 19.68万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-01-01 至 2007-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6747775
关键词：
axon cell migration fibroblast growth factor genetically modified animals gonadotropin releasing factor growth factor receptors in situ hybridization insulinlike growth factor laboratory mouse neuroendocrine system neurogenesis neuronal guidance neurons neuroregulation neurotrophic factors receptor expression tissue /cell culture

项目摘要

DESCRIPTION (provided by applicant): Gonadotropin-releasing hormone (GnRH) neurons are central to the initiation and maintenance of reproductive function in diverse vertebrates. During development, GnRH neurons enter sequential stages to mature into a functional network capable of supporting reproduction in adulthood. These stages include cell fate specification in the olfactory placodes, migration into the forebrain, and targeting of axons to the median eminence for hormone release. Signals that trigger GnRH neuronal entrance into these stages, as well as factors that regulate maturation within each stage remain largely unknown. We hypothesize that neurotrophic factors provide time-specific signals to drive the progression of GnRH neurons development. In this proposal, we will use a candidate neurotrophic factor approach and focus on the actions of a family of growth factors shown to have profound neurotrophic activities in cultured primary and immortalized GnRH neurons: the fibroblast growth factors (FGFs). Further, the actions of insulin-like growth factor I (IGF-I), a neurotrophic factor previously shown to act independently and/or collaboratively with FGF-2, will be investigated. This proposal will utilize a combination of existing transgenic models and primary GnRH neuron cultures to address the following Aims: to determine 1) if receptors for FGFs are expressed in a time-specific manner during development, 2) if FGFs alter GnRH progenitor cell expansion and the emergence of GnRH neurons, 3) if FGFs alter the migration of GnRH neurons into the forebrain, 4) if FGFs promote GnRH axon targeting, and 5) if IGF-I acts independently or synergistically with FGFs to promote the survival of GnRH neurons. Together, results from these Aims will provide important clues regarding how a neuroendocrine system critical for vertebrate reproduction develops and matures with the guidance of neurotrophic factors. Further, these results will aid in the understanding of cellular and molecular basis of developmental reproductive abnormalities that result from GnRH deficiency.

描述（由申请人提供）：促性腺激素释放激素（GNRH）神经元对于不同脊椎动物的生殖功能的启动和维持至关重要。在开发过程中，GNRH神经元进入顺序阶段，以成熟到能够支持成年后繁殖的功能网络。这些阶段包括嗅觉位置中的细胞命运规范，迁移到前脑，以及将轴突靶向激素释放的中位数。触发GNRH神经元进入这些阶段的信号，以及在每个阶段内调节成熟的因素仍然在很大程度上未知。我们假设神经营养因素提供了特定时间的信号，以推动GNRH神经元发育的发展。在此提案中，我们将使用候选神经营养因子方法，并专注于在培养的原发性和永生化的GNRH神经元中具有深刻神经营养活性的一系列生长因子的作用：成纤维细胞生长因子（FGFS）。此外，将研究一种先前证明可以独立起作用和/或与FGF-2合作的神经营养因素I（IGF-I）的作用。 This proposal will utilize a combination of existing transgenic models and primary GnRH neuron cultures to address the following Aims: to determine 1) if receptors for FGFs are expressed in a time-specific manner during development, 2) if FGFs alter GnRH progenitor cell expansion and the emergence of GnRH neurons, 3) if FGFs alter the migration of GnRH neurons into the forebrain, 4) if FGFS促进GNRH轴突靶向，5）如果IGF-I与FGF独立或协同作用以促进GnRH神经元的存活。总之，这些目标的结果将为脊椎动物繁殖至关重要的神经内分泌系统如何在神经营养因素的指导下发展和成熟。此外，这些结果将有助于理解GNRH缺乏症引起的发育生殖异常的细胞和分子基础。