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Transcriptional Networks Guiding Xenopus Development

指导非洲爪蟾发育的转录网络

基本信息

批准号：
8650900
负责人：
Julie C Baker
金额：
$ 29.67万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-15 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8650900
关键词：
Activins Affect Antibodies Behavior Beryllium Binding Biochemistry Bioinformatics Biological Biological Models Biology Cell Lineage Cells Complex DNA Data Deposition Development Embryo Embryology Embryonic Development Endoderm Endoderm Cell Flavoring Funding Gastrula Gene Expression Regulation Genetic Transcription Genomics Goals Grant In Vitro Laboratories Libraries Massive Parallel Sequencing Mediating Molecular Biology Nodal Nuclear Organism Output Pathway interactions Pattern Protein Binding Proteins Publications Regulator Genes Research Research Personnel Resources Signal Pathway Signal Transduction Signal Transduction Pathway Staging Structure Systems Biology Technology Testing Time Tissues To specify Vertebrates Xenopus blastocyst body system cell type chromatin immunoprecipitation insight knock-down new technology outreach program programs protein complex response sequence learning transcription factor xenopus development

项目摘要

DESCRIPTION (provided by applicant): Xenopus should be at the forefront of systems biology. The unique combination of biochemistry, genomics, embryology and molecular biology that can be easily used in the Xenopus embryo make it ideal for elucidating the complexities of gene regulation. We will use these strengths to explore the regulatory networks underlying endoderm specification. Endoderm is one of first cell types that emerges during embryogenesis. These cells are important for the initial patterning of the vertebrate and are the precursors to many internal organ systems. Xenopus biologists have extensively explored the signaling pathways that define endoderm; including specific signal transduction pathways like Nodal and associated downstream transcription factor cascades. Yet the gene regulatory networks (GRN) of these transcription factors and the transcriptional responses to them are still largely unexplored in any organism. Furthermore the structure and dynamic behavior of these networks within different cell lineages and through developmental time has never been examined in any vertebrate animal or in an in vitro equivalent. The power of the Xenopus embryo combined with advances in sequencing technology - primarily Chromatin Immunoprecipitation followed by Massively Parallel Sequencing (ChIPSeq) - allow the elucidation of targets used by each transcription factor and the underlying gene regulatory networks that these transcription factors define. We hypothesize that identifying the network used to specify endoderm in Xenopus will answer several important and long sought after biological questions, including what motifs - and combinations of motifs - are used by transcription factors to modulate their activity at different stages of embryogenesis and how binding of these transcription factors, alone or in combinations, correlate with expression and resulting function. We further propose to elucidate how these networks change when signaling components are removed, providing an analysis of which elements are needed for particular pathways. This resource will allow the connection of pathways and intense exploration into basic questions of Xenopus biology.

描述（由申请人提供）：非洲爪蟾应该处于系统生物学的前沿。生物化学、基因组学、胚胎学和分子生物学的独特组合可以轻松地应用于非洲爪蟾胚胎，使其成为阐明基因调控复杂性的理想选择。我们将利用这些优势来探索内胚层规范背后的调控网络。内胚层是胚胎发生过程中出现的第一种细胞类型。这些细胞对于脊椎动物的初始模式很重要，并且是许多内脏器官系统的前身。非洲爪蟾生物学家广泛探索了定义内胚层的信号通路。包括特定的信号转导途径，如 Nodal 和相关的下游转录因子级联。然而，在任何生物体中，这些转录因子的基因调控网络（GRN）以及对它们的转录反应在很大程度上仍未得到探索。此外，这些网络在不同细胞谱系内以及整个发育过程中的结构和动态行为从未在任何脊椎动物或体外等效物中进行过检查。非洲爪蟾胚胎的力量与测序技术的进步相结合——主要是染色质免疫沉淀，然后是大规模并行测序（ChIPSeq）——可以阐明每个转录因子使用的靶标以及这些转录因子定义的潜在基因调控网络。我们假设，识别用于指定非洲爪蟾内胚层的网络将回答几个重要且长期寻求的生物学问题，包括转录因子使用哪些基序和基序组合来调节其在胚胎发生的不同阶段的活性，以及这些转录因子单独或组合的结合如何与表达和产生的功能相关。我们进一步建议阐明当信号成分被去除时这些网络如何变化，从而分析特定途径需要哪些元素。该资源将允许连接途径并深入探索非洲爪蟾生物学的基本问题。