FGF SIGNALING DURING CRANIAL PLACODE DEVELOPMENT

描述（由申请人提供）：在脊椎动物中，颅感觉神经节（包括三叉神经、鳃上（EB）和侧线（LL）神经节）来源于两个来源：神经嵴和外胚层基板。颅神经的正常发育对于颅感觉系统如视觉、嗅觉、听觉、躯体感觉和味觉的形成是必不可少的。尽管它们的重要性，很少有人知道的分子机制，管理特定的颅基板的发展。我们的初步数据表明，成纤维细胞生长因子（Fgf）信号传导是EB和LL基板形成所必需的。我们将利用先进的遗传工具在斑马鱼中定义的EB和LL基板形成过程中的FGF信号转导的作用。首先，我们将建立时间和特殊要求的FGF信号，使用药理学FGF受体抑制剂和诱导型，显性阴性FGF受体转基因斑马鱼。第二，我们将确定是否需要FGF信号传导在颅基板形成的早期步骤（基板诱导和细胞迁移）或在后期步骤（神经元的增殖和存活）。最后，我们将确定EB和LL线基板的形成所需的特定的FGF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.