Gene expression in amphibian development

两栖动物发育中的基因表达

• 批准号: 9900827
• 负责人: Richard M Harland
• 金额: $ 46.29万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-06 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900827
• 关键词: Address; Amphibia; Anterior; Biochemical; Chromatin; Communities; Congenital Abnormality; Development; Disease; Embryo; Embryonic Development; Event; Evolution; Fibroblast Growth Factor; Gastrula; Gene Duplication; Gene Expression; Genes; Genetic Enhancer Element; Genetic Transcription; Genome; Goals; Grant; Hybrids; Individual; Malignant Neoplasms; Mediating; Microinjections; Microsurgery; Molecular; Pathway interactions; Pattern; Pattern Formation; Rana; Regulation; Regulator Genes; Regulatory Element; Research; Resources; Signal Transduction; Specific qualifier value; System; Testing; Work; Xenopus; chromatin immunoprecipitation; deep sequencing; egg; experimental study; gene function; gene product; human disease; improved; progenitor; programs; relating to nervous system; vertebrate genome; whole genome

ABSTRACT Our goal is to understand early vertebrate development at the molecular level. We study the problem in the frog Xenopus, whose abundant eggs are large and readily manipulated by microinjection and microsurgery. The eggs are large enough to produce material for biochemical analysis, and importantly for this project, ample material from staged and manipulated embryos or explants for deep sequencing, or chromatin for immunoprecipitation. During previous grant periods, we have identified potent signaling and signal transduction activities that contribute to embryonic development and neural induction. Recently we focused on formation of the posterior region of the embryo, which is specified by Wnt and FGF signaling in the gastrula. In parallel we improved genome assemblies and annotation for X. tropicalis and X. laevis, enabling a systems level approach. These assemblies not provide the resources necessary for hypothesis driven research for the community, but also delivered the surprising finding that after X. laevis became tetraploid through subspecies hybridization, gene losses and gene expression evolved differently between the different progenitor genomes. In the next grant period, we will determine how the Wnt and FGF pathways act on specific gene regulatory elements, in combination or individually. We will characterize genes and enhancer elements that respond to one or both signals, and test how they react to graded signals, or combinations and timing of signals, to resolve how posterior pattern formation is mediated. While the effect of timing of signaling has been documented, its contribution to the induction of distinct fates in the Anterior Posterior axis has not been addressed. In parallel work, we will move from the resource aspect of genome assembly to testing hypotheses on how genomes respond to tatraploidy. We will construct new species hybrids and ask whether they activate a “hybrid dysgenesis” program of transposon activation, and whether new transposition events occur selectively into one progenitor genome, leading to selective gene loss on that genome. We will also explore the alternative hypothesis that new chromatin marks selectively favor one genome for gene expression and gene retention over the other progenitor genome. The results of these experiments will provide basic understanding of normal vertebrate development and evolution, and potentially the mechanisms by which birth defects, and diseases of aberrant signaling, such as cancers, may arise.

摘要