ROLE OF FRIZZLED RECEPTORS AND EMBRYOGENESIS

脊椎动物的胚胎模式化是产生适当的 从多能细胞的集合细胞多样性，并涉及 一系列连续的细胞间通讯级联。 几个家庭 已经确定了分泌的蛋白质，其在发育中的作用是 在这些重要的通讯途径中充当信号分子。 在这些分子信使中，最突出的是 生长因子β（TGF-β）、hedgehog、noggin和wnt基因家族。 迄今为止，已经分离出TGF-β超家族的受体， 对其他三种受体的鉴定 重要的信号分子尚未确定。 我们有特点 来自斑马鱼的受体样分子卷曲家族成员 和非洲爪蟾来测试这些基因是否在大脑的 脊椎动物胚胎，可能作为wnt基因家族的受体 分泌的因子。 我们将继续研究这组脊椎动物fz基因家族成员， 具体目标： I. fz基因家族三个成员的分子特征 在胚胎发育过程中。 二. FZ基因在胚胎发育中的作用 使用过表达研究。 斑马鱼胚胎合子fz基因功能的研究。 四.非洲爪蟾胚胎中母体fz基因功能的测定。 诉 FZ家族介导的信号级联反应的鉴定 在胚胎发育期间。 我们将在斑马鱼和非洲爪蟾胚胎中操纵特定的fz基因 通过显微注射合成转录物异位过表达FZ 胚胎发育过程中的基因。 我们将培育出携带 fz基因突变以鉴定合子fz基因所需的途径 功能 非洲爪蟾胚胎的产生耗尽了母- 使用反义寡核苷酸表达的FZ基因将用于解决 fz基因在胚胎发生中的母性功能。 利用这些工具，我们 将识别由这个受体家族介导的信号级联反应， 像分子一样，试图在更广泛的背景下理解 这个新的基因家族在发育中起着重要作用。

Vertebrate embryonic patterning is the process of generating the proper cellular diversity from a collection of pluripotent cells and involves a series of sequential cell-cell communication cascades. Several families of secreted proteins have been identified whose role in development is to act as signaling molecules in these important communication pathways. Prominent among these molecular messengers are members of the transforming growth factor beta (TGF-beta), hedgehog, noggin, and wnt gene families. To date, receptors have been isolated for the TGF-beta superfamily, with the identification of the putative receptors for these other three important signaling molecules yet to be determined. We have characterized members of the frizzled family of receptor-like molecules from zebrafish and Xenopus to test whether these genes function in the patterning of the vertebrate embryo, serving perhaps as a receptor for the wnt gene family of secreted factors. We will pursue this set of vertebrate fz gene family members with the specific goals of: I. Molecular characterization of three members of the fz gene family during embryogenesis. II. Determination of th role of fz genes in embryonic development through the use of overexpression studies. III.Investigation of the zygotic fz gene function in zebrafish embryos. IV. Determination of maternal fz gene function in Xenopus embryos. V. Identification of the signaling cascade(s) mediated by fz family members during embryonic development. We will manipulate specific fz genes in both zebrafish and Xenopus embryos by microinjection of synthetic transcripts to ectopically overexpress fz genes during embryogenesis. We will generate zebrafish strains carrying mutations in fz genes to identify pathways required for zygotic fz gene function. The generation of Xenopus embryos depleted of a maternally- expressed fz gene using antisense oligonucleotides will be used to address the maternal function of fz genes in embryogenesis. Using these tools, we will identify the signaling cascades mediated by this family of receptor- like molecules in an attempt to understand in a broader context the role this new gene family plays in development.