ROLE OF POU DOMAIN GENES IN EARLY VERTEBRATE DEVELOPMENT

POU转录因子已被证明在 调控发育过程中细胞命运的决定。我们已经专注于 对POU结构域基因XlPOU-2功能的认识 早期神经发育。XlPOU 2紧接在 脑动蛋白的神经诱导信号通路。我们目前的目标是 鉴定XlPOU2启动子中的noggin诱导元件。我们有 通过过度表达研究了XlPOU2在Spemann的组织者中的作用 胚胎中的XlPOU2基因产物。XlPOU-2基因的过度表达 导致非洲爪哇原肠发育过程中背部基因功能的抑制 胚胎，这导致了一个“无头”的表型。因此，XlPOU2的S 这种作用似乎仅限于早期原肠胚形成。 XlPOU2干扰诱导的2度轴的形成 在WNT信号级联中。表型XlPOU2可以挽救 通过Chordin，另一种信号分子存在于组织器中。 XlPOU2阻断激活素诱导的中胚层标志物的表达，如 作为即刻反应基因，GSC。XlPOU2可能抑制GSC 因为它与GSC启动子中的两个元件结合，这两个元件都是 这些基因是III类POU基因所特有的。我们正在测试是否 XLPOU2能抑制GSC启动子的激活。 我们还在斑马鱼太极中鉴定了一个新的POU基因。这个 太极拳在发育过程中及成人脑中的表达模式 与其在规范机构方面的潜在作用一致 和/或维持神经干细胞。太极表情是 与大脑中增殖的、未分化的细胞有关。 这个细胞群可以用BrdU标记，不表达两个 神经分化标志物、乙酰化微管蛋白和 神经丝蛋白。我们正在进一步研究这些细胞的特征 使用与太极共表达的另一个标记NRP-1(一种RNA 结合蛋白)。进一步了解干细胞在人类免疫系统中的作用 在哺乳动物的发育过程中，我们正试图克隆一种与 太极。

POU transcription factors have been shown to be important in the regulation of cell fate decisions during development. We have focused on understanding the function of one POU domain gene, XlPOU 2 , in early neural development. XlPOU 2 is immediately downstream in the neural inductive signaling pathway for noggin. Our current goal is to identify noggin inducible elements in the XlPOU 2 promoter. We have examined the role of XlPOU 2 in Spemann's organizer by overexpressing the XlPOU 2 gene product in embryos. The overexpression of XlPOU 2 leads to a suppression of dorsal gene function in gastrulating Xenopus embryos, which results in a "headless" phenotype. Thus, XlPOU2's action appears to be restricted to early gastrulation. XlPOU2 interferes with the formation of a 2 degrees axis induced within the Wnt signaling cascade. The phenotype XlPOU2 can be rescued by chordin, another signaling molecule present in the organzier. XlPOU2 blocks the activin-induced expression of mesoderm markers, such as the immediate response gene, gsc. XlPOU2 may suppress gsc directly, since it binds to two elements in the gsc promoter, both of which are specific for class III POU genes. We are testing whether XLPOU2 can suppress the activation of the gsc promoter. We have also characterized a novel POU gene in zebrafish, taichi. The expression pattern of taichi during development and in the adult brain is consistent with its potential role in regulating the establishment and/or maintenance of neural stem cells. Taichi expression is associated with proliferating, non-differentiated cells of the brain. This cell population can be labeled by BrdU, and does not express two markers of neural differentiation, acetylated tubulin and neurofilament protein. We are characterizing these cells further using another marker that is co-expressed with taichi, NRP-1 (an RNA binding protein). To further understand the role of stem cells in mammalian development, we are attempting to clone a mouse homolog of taichi.