FGF Regulation of GnRH Neurons

促性腺激素释放激素（GnRH）是一种神经激素， 激活和维持生殖。合成GnRH的神经元必须 在发育过程中经历复杂的成熟过程， 系统能够支持复制。一旦成熟，GnRH系统还需要 在适当的时间内保持功能，以确保后代的繁殖。 因此，一个人的生殖健康在很大程度上取决于各种因素， GnRH系统的形成和维持。拟议研究的目标是 了解一组信号分子，成纤维细胞生长因子（FGF）， 它们的受体（FGFRs）调节发育成熟和出生后的 GnRH系统的功能。许多转基因小鼠模型，每一个都缺乏 FGF信号系统的一个独特的组成部分，将被用来调查，如果这些 缺乏导致GnRH系统的异常形成或维持， 最终导致不育。体外培养方法，形态学分析，基因 表达研究、电生理学和整个动物操作将用于 这个目的。这项研究与公共卫生高度相关，因为一个基因的突变 FGFR的表达导致以生殖失败为特征的人类疾病。 了解FGFs和FGFRs如何调节GnRH系统可以提供 对这些个体GnRH系统破坏的性质的重要见解。在 此外，它还将揭示编码FGF/FGFR的其他基因上的突变是否也是 这些人类疾病的候选人。

Gonadotropin-releasing hormone (GnRH) is a neurohomrone responsible for the activation and maintenance of reproduction. Neurons that synthesize GnRH must undergo complex maturational processes during development to become a functional system capable of supporting reproduction. Once mature, the GnRH system also needs to remain functional for an appropriate duration to ensure the propagation of offspring. Thus, one's reproductive health is critically dependent on factors that orchestrate the formation and maintenance of the GnRH system. The goal of the proposed study is to understand how a group of signaling molecules, fibroblast growth factors (FGFs), and their receptors (FGFRs) regulate the developmental maturation and postnatal functionality of the GnRH system. A number of transgenic mouse models, each lacking a distinct component of the FGF signaling system, will be used to investigate if these deficiencies result in the aberrant formation or maintenance of the GnRH system, ultimately leading to sterility. In vitro culture methods, morphological analysis, gene expression studies, electrophysiology, and whole animal manipulation will be utilized for this purpose. This research is highly relevant to public health because mutations on one of the FGFRs lead to human disorders characterized by reproductive failure. Understanding how FGFs and FGFRs regulate the GnRH system could provide important insights into the nature of GnRH system disruption in these individuals. In addition, it will reveal if mutations on other genes encoding FGFs/FGFRs are also candidates for these human disorders.