XENOPUS WNT GENES IN MESODERMAL AND NEURAL PATTERNING

爪蟾 WNT 基因在中胚层和神经模式中的作用

• 批准号: 2025491
• 负责人: Jan L Christian
• 金额: $ 8.8万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1998-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2025491
• 关键词: Xenopus; bioassay; biological signal transduction; developmental genetics; diagnosis design /evaluation; gene expression; histogenesis; mesoderm; molecular cloning; neurogenesis; phenotype; protein structure function; vertebrate embryology; Xenopus; bioassay; biological signal transduction; developmental genetics; diagnosis design /evaluation; gene expression; histogenesis; mesoderm; molecular cloning; neurogenesis; phenotype; protein structure function; vertebrate embryology

DESCRIPTION (adapted from applicant's abstract): The long term goal of the proposed research is to understand the molecular mechanisms by which Wnts convey developmental information in vertebrates. A primary goal of the present study is to examine the mechanisms by which wnt-8 contributes to abnormal or normal patterning by testing the hypotheses (a) that misexpression of Xwnt-8 in anterior mesoderm either retards the normal involution of this tissue or alters its neural inducing activity thereby leading to a loss of forebrain and (b) that misexpression of Xwnt-8 in prospective dorsal mesoderm leads to identifiable changes in gene expression that promote ventral rather than dorsal differentiation. A number of related Xenopus Wnts have been identified whose developmental functions remain unexplored. One such gene, Xwnt-8b, which is more closely related to Xwnt-8 than it is to other Wnts, is transiently expressed during the same developmental stages as Xwnt-8 but in different cell types. To initiate functional analysis of Xwnt-8b and to examine structure/function relationships to both Xwnt-8b and Xwnt-8, Dr. Christian will test the hypotheses: (a) that maintenance of the usual expression pattern of Xwnt-8b is required for normal embryonic patterning and (b) that specific, identifiable domains of Xwnt-8 and Xwnt-8b mediate their distinct biological activities and biochemical characteristics. Specific aims are: (1) analysis of mechanisms underlying the Xwnt-8 mediated loss of forebrain; (2) identification and cloning of zygotic genes involved in dorsal or ventral specification; (3) cloning of the complete coding region of the Xwnt-8b cDNA; (4) analysis of embryonic expression of Xwnt-8b transcripts; (5) perturbation of normal expression of Xwnt-8b; and (6) identification of functional domains of Xwnt-8b.

描述（改编自申请人的摘要）： 拟议的研究是了解分子机制 WNT传达脊椎动物中的发育信息。一个主要目标 本研究是检查Wnt-8的机制 通过检验假设来促进异常或正常模式 （a）在前中胚层中XWNT-8的XWNT-8的敏感性 该组织的正常情况或改变其神经诱导活性 从而导致前脑失去，（b） 前瞻性背胚层中的XWNT-8导致可识别的变化 促进腹侧而不是背分化的基因表达。 已经确定了许多相关的Xenopus Wnt 发展功能仍未开发。 一个这样的基因，xwnt-8b， 与XWNT-8相比，它与其他Wnt更紧密相关，是 在与XWNT-8相同的发育阶段瞬时表达 在不同的细胞类型中。 启动XWNT-8B和 要检查XWNT-8B和XWNT-8的结构/功能关系， 克里斯蒂安博士将检验假设：（a）维护通常 XWNT-8B的表达模式是正常的胚胎图案所必需的 （b）XWNT-8和XWNT-8B的特定，可识别的域 调解其独特的生物学活动和生化 特征。 具体目的是：（1）分析XWNT-8的机制 介导的前脑丧失； （2）合子的识别和克隆 涉及背侧或腹侧规格的基因； （3）克隆 XWNT-8B cDNA的完整编码区； （4）胚胎分析 XWNT-8B转录本的表达； （5）正常表达的扰动 XWNT-8B; （6）XWNT-8B功能域的识别。