SPECIFICATION OF THE VERTEBRATE VENTRAL NEURAL TUBE

我计划用斑马鱼来研究底板的形成， 腹侧神经管的重要组织中心。 底板 由脊索分泌的Sonic hedgehog（Shh）诱导。 然而，在这方面， 最近的研究表明，脊索并不总是必需的， 底板形成。 例如，在斑马鱼无尾（ntl）突变体中， 脊索无法区分，但地板的宽度是 实际上扩大了。 刺猬（hh）相关基因的表达也是 改变了 在野生型胚胎中，shh和虎纹刺猬（twhh）是 共表达于胚盾细胞（相当于 Xenopus organizer）。 在原肠胚形成期间，shh与Ntl共表达， 蛋白质在一个层，产生脊索;而twhh是 表示在假定产生地板的相邻层中 板 在ntl突变体中，shh和twhh表达不分离， 在原肠胚形成期间分离层。 一个假设是， 调节脊索和底板命运之间的选择，可能通过 影响原肠形成期间hh基因的表达。 我会用 分子、细胞和遗传技术在斑马鱼中的应用 为了检验以下具体假设：（1）表达TWHH的细胞 原肠胚的twhh和shh只产生底板（2） 共表达胚盾的细胞具有给予 （2）共表达twhh和shh的细胞 胚胎盾有可能产生脊索或 地板取决于他们的位置（3）Ntl转录 促进脊索分化抑制底板因子 （4）TWHH是楼板规格的基础。

I plan to use zebrafish to study the formation of the floor plate, an important organizing center in the ventral neural tube. Floor plate is induced by Sonic hedgehog (Shh) secreted by the notochord. However, recent work indicates that the notochord is not always required for floor plate formation. For example, in zebrafish no tail (ntl) mutants, notochord fails to differentiate, but the width of the floor plate is actually expanded. Expression of hedgehog (hh) related genes is also altered. In wild type embryos, shh and tiggy-winkle hedgehog (twhh) are coexpressed in cells of the embryonic shield (the equivalent of the Xenopus organizer). During gastrulation, shh is coexpressed with Ntl protein in a layer that gives rise to notochord; whereas twhh is expressed in an adjacent layer that is presumed to give rise to floor plate. In ntl mutants, shh and twhh expression do not segregate to separate layers during gastrulation. One hypothesis is that Ntl regulates a choice between notochord and floor plate fates, possibly by influencing hh gene expression during gastrulation. I will use molecular, cellular and genetic techniques available in the zebrafish to test the following specific hypotheses: (1) the twhh expressing cells of the gastrula solely give rise to floor plate (2) the twhh and shh coexpressing cells of the embryonic shield have the potential to give rise to floor plate (2) the twhh and shh coexpressing cells of the embryonic shield have the potential to give rise to either notochord or floor plate depending upon their position (3) the Ntl transcription factor promotes notochord differentiation and represses floor plate development and (4) twhh is essential for floor plate specification.