EMBRYONIC INDUCTION OF MESODERM AND NEURAL TISSUE

中胚层和神经组织的胚胎诱导

• 批准号: 3303876
• 负责人: DOUGLAS A MELTON
• 金额: $ 23.44万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3303876
• 关键词: Xenopus; cell cell interaction; complementary DNA; developmental genetics; early embryonic stage; gene expression; genetic regulation; high performance liquid chromatography; histogenesis; in situ hybridization; laboratory mouse; laboratory rabbit; mammalian embryology; mesoderm; messenger RNA; molecular cloning; neural crest; neural plate /tube; nucleic acid probes; nucleic acid sequence; polymerase chain reaction; protein purification; protein structure function; tissue /cell culture; transforming growth factors

The long term objective of the work proposed here is to understand the factors that specify cell fates, both differentiation and patterning, in early vertebrate development. Special attention is given to the induction of neural tissue. Recently, it has been shown that peptide growth factors act as morphogens or determinants in that they change the fates of cells from ectodermal to mesodermal pathways during early Xenopus development. Two embryonic peptide growth factors, fibroblast growth factor and the Vgl protein, are involved in mesoderm induction. It is also known that at least one other factor is needed to account for all the mesodermal cell types that are formed. This other factor is likely to be a member of he transforming growth factor beta family and may be the inducing factor secreted from XTC cells, XTC-MIF. We have now cloned several new members of the TGFbeta gene family, in Xenopus, one of which may be the XTC-MIF gene. We propose to study the expression these new TGFbeta genes in early development and determine their roles in mesodermal and/or neural induction. A second major aspect of the proposal stems from our discovery of a neural inducing factor. This factor, secreted from a murine macrophage cell line, induces neural tissue in isolated Xenopus ectodermal cells that would otherwise form only ciliated epidermis. Animal caps treated with PIF organize the induced dorsal CNS and mesodermal tissues into a clear axis with antero-posterior polarity. Taken together, these findings suggest that PIF has many of the properties associated with a Spemann organizer. We propose to purify the PIF protein, clone the gene encoding its Xenopus homologue and study the function and expression of this novel neural inducing factor.

这里提出的工作的长期目标是了解 这些因素决定了细胞的命运，包括分化和模式化， 早期脊椎动物发育 特别注意的是， 的神经组织。 最近，已经表明肽生长因子作为形态发生剂 或决定因素，因为它们改变了细胞的命运， 非洲爪蟾早期发育过程中的中胚层途径。 两个先天胎 肽生长因子、成纤维细胞生长因子和Vg 1蛋白， 参与中胚层诱导。 还已知的是，至少一个其他的 需要考虑所有中胚层细胞类型， 形成了 这另一个因素很可能是他转变的一个成员， 可能是XTC分泌的诱导因子 细胞，XTC-MIF。 我们现在已经克隆了TGF β基因的几个新成员 XTC-MIF基因可能是非洲爪蟾中的一个家族。 我们建议 研究这些新的TGF β基因在早期发育中的表达， 确定它们在中胚层和/或神经诱导中的作用。 该提议的第二个主要方面源于我们发现了一种神经 诱发因素 该因子由鼠巨噬细胞系分泌， 在分离的非洲爪蟾外胚层细胞中诱导神经组织， 否则只形成纤毛表皮。 用PIF处理的动物帽 将诱导的背侧中枢神经系统和中胚层组织成清晰的轴 具有前后极性。 综上所述，这些发现表明 PIF有许多与Spemann组织者相关的属性。 我们拟纯化PIF蛋白，克隆其编码基因， 同源，并研究这种新的神经元的功能和表达 诱发因素