FGF SIGNALING DURING CRANIAL PLACODE DEVELOPMENT

描述(申请人提供)：在脊椎动物中，脑感觉神经节，包括三叉神经节、鳃上神经节(EB)和侧线神经节(LL)，来自两个来源：神经脊和外胚层安慰剂。脑神经的正常发育对形成视觉、嗅觉、听觉、躯体感觉和味觉等颅脑感觉系统至关重要。尽管它们很重要，但人们对控制特定颅骨安慰剂发育的分子机制知之甚少。我们的初步数据表明，成纤维细胞生长因子(成纤维细胞生长因子)信号在EB和LL安慰剂的形成中是必需的。我们将利用斑马鱼中先进的遗传工具来确定成纤维细胞生长因子信号在EB和LL安慰剂形成过程中的作用。首先，我们将使用药理上的成纤维细胞生长因子受体抑制剂和可诱导的显性负性成纤维细胞生长因子受体转基因斑马鱼来建立成纤维细胞生长因子信号的时间和特殊要求。其次，我们将确定在颅骨胎盘形成的早期阶段(胎盘诱导和细胞迁移)还是在后期步骤(神经元的增殖和存活)中是否需要成纤维细胞生长因子信号。最后，我们将确定形成EB和LL线胎盘所需的特定的成纤维细胞生长因子配体。

DESCRIPTION (provided by applicant): In vertebrates, cranial sensory ganglia, including trigeminal, epibranchial (EB), and lateral line (LL) ganglia, derive from two sources: neural crest and ectodermal placodes. The proper development of cranial nerves is essential for the formation of cranial sensory systems such as vision, smell, hearing, somatosensation, and taste. Despite their importance, very little is known about molecular mechanisms that govern the development of specific cranial placodes. Our preliminary data indicate that fibroblast growth factor (Fgf) signaling is required for the formation of EB and LL placodes. We will take advantage of advanced genetic tools in zebrafish to define roles for Fgf signaling during formation of EB and LL placodes. First, we will establish temporal and special requirements for Fgf signaling using pharmacologic Fgf-receptor inhibitor and inducible, dominant-negative Fgf-receptor transgenic zebrafish. Second, we will determine whether Fgf signaling is required during early steps of cranial placodes formation (placode induction and cell migration) or during later steps (proliferation and survival of neurons). Finally, we will identify specific Fgf ligands that are required for the formation of EB and LL line placodes.