HOMEOBOX GENES AND THEIR TARGETS IN XENOPUS DEVELOPMENT

非洲爪蟾发育中的同源盒基因及其靶点

• 批准号: 6215323
• 负责人: EDWARD M DE ROBERTIS
• 金额: $ 7.05万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6215323
• 关键词: Xenopus; alternatives to animals in research; body regions; cell differentiation; developmental genetics; ectoderm; embryogenesis; endoderm; gene expression; gene induction /repression; genetically modified animals; homeobox genes; immunoprecipitation; in situ hybridization; mesoderm; messenger RNA; microinjections; molecular cloning; nucleic acid sequence; regulatory gene; transfection; vertebrate embryology

Homeobox genes encode DNA-binding proteins that control key steps in animal development. Spemann and Mangold (1924) identified the dorsal lip of the blastopore, the organizer, as a region of the embryo able to induce twinning, or a secondary body axis, when transplanted to a host embryo. Recent experiments indicate that homeobox genes, such as goosecoid and Xnot-2, play an important role in the organizer phenomenon. Microinjection of goosecoid mRNA can mimic Spemann's experiment, recruiting neighboring cells into twinned axes in Xenopus. Because homeobox genes encode nuclear proteins, their effects on neighboring cells must be mediated by secreted molecules. We have recently identified the two major downstream targets activated by organizer homeobox genes: chordin and cerberus. Both are novel secreted proteins. In addition, goosecoid represses the expression of BMP-4, a ventralizing signal that is antagonized by the chordin protein. By studying organizer-specific homeobox genes and their secreted targets chordin, cerberus and BMP-4 we hope to better understand the molecular mechanisms that pattern vertebrate development. In particular, we will ask how these genes pattern the three germ layers, the mesoderm, the ectoderm and the endoderm, and how they control the sequential deployment of Hox genes in the antero-posterior body axis. Because the molecular mechanisms of development are very conserved, these studies in Xenopus should provide insights into the molecules that control development in all vertebrates, including humans.

同源框基因编码的DNA结合蛋白控制着 动物发育。Spemann和Mangold(1924)发现了背部 胚孔的唇，组织者，作为胚胎能区的一部分 移植到胚胎上时，会导致双胞胎或第二体轴 寄主胚胎。最近的实验表明，同源盒基因，如 Goosecid和XNOT-2在组织者中扮演着重要的角色 现象。微量注射类鹅类基因可以模拟Spemann氏病 实验，将非洲爪哇的相邻细胞招募成孪生轴。 由于同源盒基因编码核蛋白，它们对 邻近的细胞必须由分泌的分子来调节。我们有 最近确定了由激活的两个主要下游目标 组织者同源盒子基因：Chordin和Cerberus。两者都是新奇的秘密 蛋白质。此外，鹅膏还抑制BMP-4的表达。 被Chordin蛋白拮抗的腹壁信号。 通过研究组织者特有的同源异型盒基因及其分泌 靶标Chordin、Cerberus和BMP-4我们希望更好地了解 形成脊椎动物发育模式的分子机制。在……里面 具体地说，我们会问这些基因是如何排列三个胚芽层的， 中胚层、外胚层和内胚层，以及它们如何控制 HOX基因在体轴前后的顺序部署。 因为发育的分子机制非常保守， 对非洲爪哇的这些研究应该会提供对分子的洞察 控制着包括人类在内的所有脊椎动物的发育。