SPECIFICATION OF THE VERTEBRATE VENTRAL NEURAL TUBE

我计划用斑马鱼来研究地板的形成，一个 腹侧神经管的重要组织中心。地板 是由脊索分泌的Sonic Hedgehog(Shh)诱导的。然而， 最近的研究表明，脊索并不总是需要的 楼板形成。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 实际上是扩大了。刺猬(HH)相关基因的表达 被更改了。在野生型胚胎中，Shh和Tiggy-winkle Hedgehog(TWHH)是 在胚盾细胞中共表达(相当于 非洲爪哇组织者)。在原肠发育过程中，shh与ntl共表达。 产生脊索的层中的蛋白质；而TWHH是 在相邻的层中表达，该层被认为会产生地板 盘子。在ntl突变体中，shh和twhh的表达不分离到 在原肠形成过程中分离各层。一种假设是NTL 调节脊索和地板命运之间的选择，可能是通过 原肠发育过程中对HH基因表达的影响。我会用 斑马鱼的分子、细胞和遗传技术 为了检验以下具体假设：(1)表达TWHH的细胞 原肠胚单生底板(2)TWH和SHH 胚胎盾牌的共表达细胞有可能为 升至底板(2)TWHH和SHH共表达的细胞 胚胎盾牌有可能形成脊索或脊索 底板取决于它们的位置(3)NTL转录 因子促进脊索分化，抑制底板 发展和(4)TWHH是地板规范必不可少的。

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.