XENOPUS WNT GENES IN MESODERMAL AND NEURAL PATTERNING

描述（改编自申请人的摘要）：长期目标 拟议的研究是了解分子机制， Wnt在脊椎动物中传递发育信息。的主要目标 本研究旨在探讨Wnt-8在大鼠肝细胞中的作用机制。 通过检验假设， (a)Xwnt-8在前中胚层的错误表达， 该组织的正常退化或改变其神经诱导活性 从而导致前脑的损失，以及（B） Xwnt-8在预期的背中胚层导致可识别的变化， 促进腹侧而不是背侧分化的基因表达。 一些相关的爪蟾Wnt已被确定， 发育功能尚未探索。 其中一个基因Xwnt-8b， 它与Xwnt-8的关系比与其他Wnt的关系更密切， 在与Xwnt-8相同的发育阶段瞬时表达， 在不同的细胞类型。 启动Xwnt-8b的功能分析， 为了检查与Xwnt-8b和Xwnt-8两者的结构/功能关系， 博士基督教将测试的假设：（一），维护通常的 Xwnt-8b的表达模式是正常胚胎形成所必需的 和（B）Xwnt-8和Xwnt-8 B特异性可识别结构域 介导其独特的生物活性和生物化学 特色 具体目标是：（1）分析Xwnt-8的机制 介导的前脑缺失;（2）合子的鉴定和克隆 参与背侧或腹侧特化的基因;（3）克隆 Xwnt-8b cDNA的完整编码区;（4）胚胎发育分析 Xwnt-8b转录本的表达;（5）正常表达的干扰 （6）Xwnt-8b的功能结构域的鉴定。

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.