XNF7 AND AXIS DETERMINATION

参与建立的分子的鉴定 胚胎轴是脊椎动物研究的重要问题之一 发展最近，许多生长因子如激活素，FGF， 和BMP以及分泌因子如Xwnts和noggin 在轴向图案中扮演重要角色。很可能，许多 这些用来建立早期胚胎的预模式， 通过信号传导途径激活区域特异性基因 如goosecoid、Xlim、Xnot、Xbra等。因此 对于鉴定作为中间体的其他分子是很重要的 在信号转导途径和激活区域之间- 特异性基因表达XNF 7是一种母源表达蛋白， 在卵母细胞GV和成熟过程中释放到细胞质中。是 保留在细胞质中，直到中期囊胚过渡（MBT）时， 进入细胞核。xnf 7的显性负性形式的过表达 （xnf 7thr-glu），其抑制内源性xnf 7进入 在MBT核的背腹轴缺陷的结果。我们的假设 XNF 7作为生长因子信号 转导途径和原肠胚阶段基因的激活。 我们打算通过完成以下任务来检验这一假设：（l） 表征调节xnf 7功能的遗传途径（2）为了进一步 表征xnf 7thr-glu突变体表型和（3）鉴定 与xnf 7相互作用并鉴定xnf 7 DNA结合的分子 绝佳的价钱xnf 7thr-glu突变体产生显性阴性的能力 表型为我们提供了一个工具，以探讨广泛的问题，背- 早期胚胎的腹侧图案。这种分析很可能 将证实先前描述的分子的作用，并允许我们 发现参与这一过程的新分子，从而进一步提供 深入了解脊椎动物中轴模式的分子基础。这 这项研究还将揭示细胞异常生长的机制 以及癌症和出生缺陷等疾病的分化。

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.