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）：Xenopus应该位于系统生物学的最前沿。可以轻松用于Xenopus Embryo的生物化学，基因组学，胚胎学和分子生物学的独特组合使其非常适合阐明基因调节的复杂性。我们将利用这些优势探索内胚层规范基础的监管网络。内胚层是胚胎发生过程中首次出现的细胞类型之一。这些细胞对于脊椎动物的初始图案很重要，并且是许多内部器官系统的前体。 Xenopus生物学家已广泛探索了定义内胚层的信号传导途径。包括特定的信号转导途径，例如节点和相关的下游转录因子级联。然而，这些转录因子的基因调节网络（GRN）以及对它们的转录反应在任何生物体中仍未探索。此外，这些网络在不同的细胞谱系中以及在发育时间内的结构和动态行为从未在任何脊椎动物的动物或体外等效物中进行检查。爪蟾胚胎的功率与测序技术的进步相结合 - 主要是染色质免疫沉淀，然后是大规模平行测序（Chipseq） - 允许阐明每个转录因子使用的靶标以及这些转录因子定义这些转录因子的基因调控网络。我们假设，识别用于Xenopus中内胚层的网络将回答几个重要且长期以来一直在追求的生物学问题，包括转录因子在不同的胚胎发生阶段的活性以及这些转录因子的不同阶段以及与组合中的结合，与表达和结果表达功能相呼应。我们进一步建议在删除信号传导组件时阐明这些网络如何变化，从而分析特定途径需要哪些元素。该资源将允许将途径和强烈探索与Xenopus生物学的基本问题联系起来。