XNF7 AND AXIS DETERMINATION

分子的鉴定涉及到建立 胚轴是脊椎动物最重要的问题之一。 发展。近年来，激活素、成纤维细胞生长因子、 BMP以及Xwnts和noggin等分泌因子 在轴向图案化中发挥重要作用。很可能很多人 这些有助于建立早期胚胎的前置模式并进行操作 通过信号转导途径激活区域特异性基因 如原肠胚期的鹅类、Xlim、Xnot、Xbra等。因此，它 对于识别作为中间体的其他分子很重要 在信号转导通路和区域激活之间- 特定的基因表达。XNF7是一种母体表达的蛋白质，它是 在卵母细胞GV中，在成熟过程中释放到细胞质中。它是 保留在细胞质中，直到中期囊胚过渡(MBT)时 进入原子核。显性否定形式XNF7的过度表达 (xnf7thr-Glu)，抑制内源性xnf7进入 位于MBT处的核导致背腹侧轴向缺陷。我们的假设 是XNF7在生长因子-信号之间起中介作用 原肠胚期的转导途径和基因的激活。 我们打算通过完成以下工作来验证这一假设：(L) 表征调控XNF7功能的遗传途径(2)以进一步 鉴定xnf7thr-Glu突变表型和(3)鉴定 与xnf7相互作用并识别xnf7 DNA结合的分子 地点。XNF7THR-Glu突变体产生显性负值的能力 表型为我们提供了一个探索背部广泛问题的工具- 早期胚胎的腹侧花纹。很可能这一分析 将确认前面描述的分子的作用，并允许我们 发现参与这一过程的新分子，从而进一步提供 对脊椎动物轴向模式的分子基础的洞察。这 研究还将阐明细胞异常生长的机制 以及与癌症和出生缺陷等疾病有关的分化。

The identification of molecules involved in the establishment of the embryonic axis is one of the most important problems in vertebrate development. Recently, a number of growth factors such as activins, FGF, and BMPs as well as secreted factors such as Xwnts and noggin were shown to play important roles in axial patterning. It is likely that many of these serve to establish the prepatterning of the early embryo and operate through signal transduction pathways to activate region-specific genes such as goosecoid, Xlim, Xnot, Xbra at the gastrula stage. Therefore, it is important to identify other molecules that serve as intermediates between the signal transduction pathways and the activation of region- specific gene expression. Xnf7 is a maternally expressed protein that is in the oocyte GV and released into the cytoplasm during maturation. It is retained in the cytoplasm until the mid-blastula transition (MBT) when it enters the nucleus. Overexpression of a dominant negative form of xnf7 (xnf7thr-glu) that inhibits the entry of the endogenous xnf7 into the nucleus at the MBT results in dorsal-ventral axial defects. Our hypothesis is that xnf7 serves as an intermediate between the growth factor-signal transduction pathways and the activation of genes at the gastrula stage. We intent to test this hypothesis by accomplishing the following: (l) To characterize the genetic pathway regulating xnf7 function (2) To further characterize the xnf7thr-glu mutant phenotype and (3) To identify molecules that interact with xnf7 and to identify the xnf7 DNA binding site. The ability of xnf7thr-glu mutant to produce a dominant negative phenotype provides us with a tool to explore the broad issue of dorsal- ventral patterning of the early embryo. It is likely that this analysis will confirm the role of previously described molecules and permit us to discover new molecules involved in this process thereby providing further insights into the molecular basis of axial patterning in vertebrates. This study will also shed light on mechanisms involved in abnormal cell growth and differentiation involved in diseases such as cancer and birth defects.