Experimental solution of the GRN underlying development of the chick neural crest
雏鸡神经嵴发育的GRN基础实验解决方案
基本信息
- 批准号:7751732
- 负责人:
- 金额:$ 29.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-01 至 2014-05-31
- 项目状态:已结题
- 来源:
- 关键词:Antisense OligonucleotidesBindingBinding SitesBioinformaticsBiological AssayCartilageCellsChick EmbryoDataDevelopmentDevelopmental GeneDevelopmental ProcessEctodermElectrophoretic Mobility Shift AssayEmbryoEnhancersFaceFamilyFibroblast Growth FactorGenesGenetic Enhancer ElementGenomeGenomicsGoalsHumanImageIn Situ HybridizationMammalsMethodologyMothersMusMutationNatureNeural CrestNeural Crest CellNeural tubeNeuronsNucleic Acid Regulatory SequencesPathway interactionsPhasePopulationPositioning AttributeProcessPropertyRegulator GenesRegulatory ElementRoleSea UrchinsSensorySequence AnalysisSignal TransductionSiteSnailsSolutionsSpecific qualifier valueSpeedStagingSystemTechnologyTestingUp-RegulationXenopusZebrafishcell typechromatin immunoprecipitationcomparativedata acquisitioneggfeedinggene discoverygene interactionloss of functionmelanocyteneural platenovelprogenitorprospectiverelating to nervous systemslugsuccesstooltranscription factor
项目摘要
By adapting approaches that have been applied with great success to testing the sea urchin developmental gene
regulatory network, we propose to perform a detailed analysis of the gene interactions involved in specifying vertebrate
neural crest cells. Our aim is to understand the genomic control of this process at a systems level by revealing most/all
of the inputs into the system and methodically functionally perturbing them to examine interactions amongst players.
In other words, we propose to test a putative neural crest gene regulatory network (NC-GRN) at a systems levels in a
single vertebrate. These efforts will be greatly facilitated by the advent of new, high speed technologies that will
significantly increase the rate of data acquisition and interpretation as well as novel bioinformatics tools to interrogate
genomic information. We will draw heavily on methodologies and concepts developed in the Davidson lab. The goal
is to apply these to a vertebrate system at moderate to high throughput. This represents a huge leap forward in both the
scale and depth of what can be tested. The recent availability of the chick genome affords a rich tool for discovery of
genes and regulatory regions. In addition as an amniote, chick development is similar to humans and, unlike mammals,
is accessible to imaging at early stages since the embryo develops outside the mother. We will test linkages in the chick
neural crest gene regulatory network, identify regulatory elements and test direct interactions.
Aim 1: Examine effects of loss-of-function of known neural plate border and neural crest specifiers.
By introducing morpholino antisense oligonucleotides into the prospective neural plate border or closing neural
tube. Effects on potential downstream targets will be examined by in situ hybridization and QPCR.
Aim 2: Test the function of newly identified transcription factors in the NC-GRN
We will test the role and position additional transcription factors in the network and we will continue to attempt to
identify transcription factors that feed into the NC-GRN.
Aim 3: Isolate regulatory regions of neural crest specifer and downstream targets.
We will isolate putative regulatory regions of neural crest specifier genes, initially for Sox 10 and then other
specifiers, via comparative sequence analysis. Candidate regions will be electroporated into early chick embryos to
identify neural crest regulatory elements.
Aim 4: Establish direct relationships within the network by identification of transcription factor
binding sites within regulatory regions of downstream genes.
We will interrogate the regulatory regions of neural crest enhancer elements for critical sequences responsible for
binding of neural plate border specifiers genes and/or neural crest specifier genes. We will assay for direct binding
interactions within the network using chromatin immunoprecipitation assay, electrophoretic mobility shift assays and
mutational analysis.
通过采用已经成功应用于测试海胆发育基因的方法,
调控网络,我们建议进行详细的分析基因的相互作用,参与指定脊椎动物
神经嵴细胞我们的目标是通过揭示大多数/所有的基因组控制,在系统水平上了解这一过程
系统的输入,并有系统地功能扰动它们,以检查玩家之间的互动。
换句话说,我们建议在系统水平上测试一个假定的神经嵴基因调控网络(NC-GRN),
单一脊椎动物。新的高速技术的出现将大大促进这些努力,
显着提高数据采集和解释的速度以及新的生物信息学工具来询问
基因组信息我们将大量借鉴戴维森实验室开发的方法和概念。目标
是将这些应用于脊椎动物系统中的中到高通量。这代表了一个巨大的飞跃,
可以测试的范围和深度。最近鸡基因组的可用性为发现
基因和调控区。此外,作为一种哺乳动物,小鸡的发育与人类相似,与哺乳动物不同,
由于胚胎在母体外发育,因此在早期阶段可以进行成像。我们将在幼鸟体内测试
神经嵴基因调控网络,确定调控元件和测试直接相互作用。
目的1:检查已知神经板边界和神经嵴指定符的功能丧失的影响。
通过将吗啉代反义寡核苷酸引入到预期的神经板边缘或闭合神经板,
管材.将通过原位杂交和QPCR检查对潜在下游靶标的影响。
目的2:检测新发现的转录因子在NC-GRN中的功能
我们将测试网络中其他转录因子的作用和位置,我们将继续尝试
鉴定进入NC-GRN的转录因子。
目的3:分离神经嵴特异性蛋白调控区及其下游靶点。
我们将分离神经嵴特异性基因的假定调控区域,首先是Sox 10,然后是其他基因。
说明符,通过比较序列分析。将候选区域电穿孔到早期鸡胚中,
鉴定神经嵴调节元件。
目的4:通过识别转录因子在网络中建立直接关系
下游基因调控区域内的结合位点。
我们将询问神经嵴增强子元件的调控区,寻找负责
神经板边界指定基因和/或神经嵴指定基因的结合。我们将检测直接结合
使用染色质免疫沉淀分析、电泳迁移率变动分析和
突变分析
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Marianne Bronner其他文献
Marianne Bronner的其他文献
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{{ truncateString('Marianne Bronner', 18)}}的其他基金
Contribution of the sacral neural crest to the peripheral nervous system of the post-umbilical gastrointestinal tract
骶神经嵴对脐后胃肠道周围神经系统的贡献
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10644256 - 财政年份:2023
- 资助金额:
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Transcriptional regulation of neuronal cell lineage decisions in the developing enteric nervous system
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10444843 - 财政年份:2022
- 资助金额:
$ 29.75万 - 项目类别:
Transcriptional regulation of neuronal cell lineage decisions in the developing enteric nervous system
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- 批准号:
10646306 - 财政年份:2022
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Cell lineage and transcriptional analysis of the vertebrate neural plate border
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10178170 - 财政年份:2020
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Progressive acquisition of novel neural crest derivatives along the neural axis during vertebrate evolution
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- 批准号:
10397520 - 财政年份:2019
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Progressive acquisition of novel neural crest derivatives along the neural axis during vertebrate evolution
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- 批准号:
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Cell lineage and transcriptional analysis of the vertebrate neural plate border
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