Role of a Novel EGF-Related Growth Factor in Mouse Gastrulation

新型 EGF 相关生长因子在小鼠原肠胚形成中的作用

• 批准号: 9630903
• 负责人: Michael Shen
• 金额: $ 30万
• 依托单位: Rutgers, The State University of New Jersey-RBHS-Robert Wood
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9630903&HistoricalAwards=false
• 关键词: Role; Novel; EGF; Related; Growth

9630903 Shen To understand the molecular mechanisms that regulate embryonic pattern formation and differentiation, it is necessary to identify candidate growth factors that may be involved in these processes, and to characterize their functional properties. Previous studies of mouse embryogenesis in this laboratory have used a differential display screening approach to identify mesoderm-specific genes expressed during the differentiation of embryonic stem (ES) cells in culture. This strategy has resulted in the isolation of a novel gene named Cryptic, which encodes a potentially secreted molecule containing a single copy of an epidermal growth factor-like (EGF) motif. Analysis of Cryptic expression indicates that it is expressed during gastrulation in two distinct spatial domains, which correspond to the axial mesoderm and to the lateral plate mesoderm. Thus, the novel gene Cryptic encodes a potential signaling molecule that has an expression pattern consistent with a role in mesoderm patterning and differentiation. Notably, Cryptic appears to be a member of a new family of EGF-related growth factors. The Cryptic gene was originally named on the basis of its significant sequence similarities with the Cripto gene, which is also expressed during mesoderm formation and has growth stimulating activities in cell culture. The Cryptic gene is also related to a recently described Xenopus gene named FRL-1, which has mesoderm - and neural-inducing activities in embryonic assays, and can activate fibroblast growth factor IFGF) receptors. Based on (1) the sequence similarities between Cryptic, Cripto, and FRL-1, (2) the growth factor activity of Cripto, (3) the mesoderm and neural-inducing activities of FRL-1, (4) the activation of FGF receptors by FRL-1, and (5) the spatially and temporally restricted pattern of Cryptic expression, it is likely that Cryptic encodes a potential signaling molecule that may be involved in cellular interactions during embryonic pattern formation and cell fate det ermination. To address this hypothesis, the proposed research will investigate the biological and biochemical properties of Cryptic, organized around three specific aims: (1) Characterization of Cryptic mRNA and protein expression patterns, (2) Investigation of the biochemical properties and function of CRYPTIC protein and its receptor, and (3) Analysis of biological requirements for Cryptic during mouse development. Taken together, these studies will synergize to provide a greater understanding of the biological and biochemical functions of this novel growth factor-like molecule, and perhaps those related family members. Furthermore, these investigations may lead to insights concerning the molecular mechanisms involved in growth factor signaling during embryonic patterning and differentiation in vertebrate development.

9630903 Shen了解调节胚胎模式形成和分化的分子机制，有必要确定可能涉及这些过程中的候选生长因子，并表征其功能性能。 先前对该实验室中小鼠胚胎发生的研究使用了差异显示筛选方法来识别在培养物中胚胎茎（ES）细胞分化过程中表达的中胚层特异性基因。 该策略导致了一个名为Cryptic的新型基因的分离，该基因编码了一个潜在分泌的分子，该分子包含表皮生长因子样（EGF）基序的单个拷贝。 对神秘表达的分析表明，在两个不同的空间结构域中胃表达，与轴向中胚层相对应，对应于轴向板中的中胚层。 因此，新型基因隐秘编码具有与中胚层模式和分化相一致的表达模式的潜在信号分子。 值得注意的是，神秘主义者似乎是与EGF相关增长因素的新家族的成员。 该隐性基因最初是基于其与Cripto基因的显着序列相似性命名的，该基因在中胚层形成过程中也表达，并且在细胞培养中具有生长刺激活性。 神秘基因也与最近描述的爪蟾基因相关，该基因称为FRL-1，该基因在胚胎分析中具有中胚层和神经诱导活性，并且可以激活成纤维细胞生长因子IFGF受体。 Based on (1) the sequence similarities between Cryptic, Cripto, and FRL-1, (2) the growth factor activity of Cripto, (3) the mesoderm and neural-inducing activities of FRL-1, (4) the activation of FGF receptors by FRL-1, and (5) the spatially and temporally restricted pattern of Cryptic expression, it is likely that Cryptic encodes a potential signaling molecule that may be involved in cellular胚胎模式形成和细胞命运过程中的相互作用。 为了解决这一假设，拟议的研究将研究隐秘的生物学和生物化学特性，围绕三个具体目的组织：（1）隐秘mRNA和蛋白质表达模式的表征，（2）研究生化特性和隐秘蛋白质及其受体的功能以及其受体的功能，以及（3）对小鼠开发的生物学需求分析。 综上所述，这些研究将协同作用，以更深入地了解这种新型生长因子样分子的生物学和生化功能，也许会提供那些相关的家庭成员。 此外，这些研究可能会导致有关在胚胎构图和脊椎动物发育中分化过程中与生长因子信号传导相关的分子机制的见解。