Tissue-specific roles for Foxa2 during cardiac development and function
Foxa2 在心脏发育和功能过程中的组织特异性作用
基本信息
- 批准号:7330100
- 负责人:
- 金额:$ 4.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-01 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAllelesAnteriorBilateralBiological AssayBoxingCardiacCardiac conduction systemCell LineageComplexCongenital AbnormalityCongenital Heart DefectsCoupledDataDefectDevelopmentDiseaseEchocardiographyElectrocardiogramEmbryoEndodermFunctional disorderFutureGene ExpressionGenesGenetic Predisposition to DiseaseHeartHeart AtriumHumanImmunohistochemistryIn Situ HybridizationIncidenceIsomerismLacZ GenesLeadLeftLifeLive BirthMediatingMesodermMolecularMolecular ProfilingMolecular TargetMusMutagenesisMutant Strains MiceNaturePathway interactionsPatternPhenotypePrevalencePrimitive foregut structurePrimordiumProcessReporterRoleSecondary toSideSinoatrial NodeSitus InversusStagingStructureSyndromeSystemTherapeuticTimeTissuesTransgenesTransgenic OrganismsWinged Helixbasecardiogenesiscell typecongenital heart disorderdesignheart functionimprovedinsightmalformationmolecular asymmetrymutantnovelpostnataltranscription factor
项目摘要
DESCRIPTION (provided by applicant): Congenital heart anomalies reflect the most common form of birth defect, present in almost 1 % of all live births. Malformations of the cardiac conduction system often lead to serious afflictions that can become life-threatening with little warning while syndromes involving defective establishment of left-right asymmetry are frequently manifest in abnormal cardiac structure and can be incompatible with survival into adulthood. The transcription factor Foxa2 is expressed in endodermal and mesodermal domains known to influence cardiac development. Preliminary data obtained by combining a conditional Foxa2 deletion allele with tissue-specific Cre-expressing lines suggest critical roles for Foxa2 in multiple distinct aspects of cardiogenesis, including left-right patterning, cardiac conduction, and postnatal heart function. Specific Aim 1 is designed to explore the requirement for Foxa2 in endoderm during early cardiogenesis. A gene expression analysis, including in situ hybridization, will be used to define the downstream targets and molecular pathways that mediate Foxa2 function in this tissue. In Specific Aim 2, the postnatal phenotype of mesodermal-specific Foxa2 mutants will be characterized. These studies will be coupled with an expression analysis designed to uncover the molecular defects that underlie the cardiac phenotype, and to define the role of Foxa2 in these pathways. Understanding the pathways within which Foxa2 regulates cardiac development will provide insight into the genetic etiology of human cardiac malformations involving the conduction system and left-right asymmetry. Relevance: The proposed study will use mutant mice to investigate how the Foxa2 gene is involved in the asymmetrical development of a heart with unique right and left-sided qualities. We will also examine the role of Foxa2 in the formation of specialized tissues that propagate and conduct the electrical impulses which generate a coordinated heart beat. The results of these studies will impact our understanding of birth defects in which the heart is formed abnormally or has an irregular beat.
描述(由申请人提供):先天性心脏异常反映了最常见的出生缺陷形式,几乎占所有活产婴儿的1%。心脏传导系统的畸形通常会导致严重的疾病,在没有任何预警的情况下可能危及生命,而涉及左右不对称建立缺陷的综合征通常表现为心脏结构异常,并且可能与成年后的生存不相容。转录因子Foxa2在已知影响心脏发育的内胚层和中胚层区域表达。通过将条件Foxa2缺失等位基因与组织特异性cre表达系结合获得的初步数据表明,Foxa2在心脏发生的多个不同方面发挥着关键作用,包括左右模式、心脏传导和出生后心脏功能。特异性Aim 1旨在探讨早期心脏发生过程中内胚层对Foxa2的需求。包括原位杂交在内的基因表达分析将用于确定介导Foxa2在该组织中的功能的下游靶点和分子途径。在Specific Aim 2中,中胚层特异性Foxa2突变体的出生后表型将被表征。这些研究将与表达分析相结合,旨在揭示构成心脏表型的分子缺陷,并确定Foxa2在这些途径中的作用。了解Foxa2调节心脏发育的途径将有助于深入了解涉及传导系统和左右不对称的人类心脏畸形的遗传病因。相关性:这项拟议的研究将使用突变小鼠来研究Foxa2基因如何参与具有独特左右侧特征的心脏的不对称发育。我们还将研究Foxa2在特殊组织形成中的作用,这些组织负责传播和传导产生协调心跳的电脉冲。这些研究的结果将影响我们对出生缺陷的理解,即心脏形成不正常或跳动不规律。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Zachary Harrelson其他文献
Zachary Harrelson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
Linkage of HIV amino acid variants to protective host alleles at CHD1L and HLA class I loci in an African population
非洲人群中 HIV 氨基酸变异与 CHD1L 和 HLA I 类基因座的保护性宿主等位基因的关联
- 批准号:
502556 - 财政年份:2024
- 资助金额:
$ 4.27万 - 项目类别:
Olfactory Epithelium Responses to Human APOE Alleles
嗅觉上皮对人类 APOE 等位基因的反应
- 批准号:
10659303 - 财政年份:2023
- 资助金额:
$ 4.27万 - 项目类别:
Deeply analyzing MHC class I-restricted peptide presentation mechanistics across alleles, pathways, and disease coupled with TCR discovery/characterization
深入分析跨等位基因、通路和疾病的 MHC I 类限制性肽呈递机制以及 TCR 发现/表征
- 批准号:
10674405 - 财政年份:2023
- 资助金额:
$ 4.27万 - 项目类别:
An off-the-shelf tumor cell vaccine with HLA-matching alleles for the personalized treatment of advanced solid tumors
具有 HLA 匹配等位基因的现成肿瘤细胞疫苗,用于晚期实体瘤的个性化治疗
- 批准号:
10758772 - 财政年份:2023
- 资助金额:
$ 4.27万 - 项目类别:
Identifying genetic variants that modify the effect size of ApoE alleles on late-onset Alzheimer's disease risk
识别改变 ApoE 等位基因对迟发性阿尔茨海默病风险影响大小的遗传变异
- 批准号:
10676499 - 财政年份:2023
- 资助金额:
$ 4.27万 - 项目类别:
New statistical approaches to mapping the functional impact of HLA alleles in multimodal complex disease datasets
绘制多模式复杂疾病数据集中 HLA 等位基因功能影响的新统计方法
- 批准号:
2748611 - 财政年份:2022
- 资助金额:
$ 4.27万 - 项目类别:
Studentship
Genome and epigenome editing of induced pluripotent stem cells for investigating osteoarthritis risk alleles
诱导多能干细胞的基因组和表观基因组编辑用于研究骨关节炎风险等位基因
- 批准号:
10532032 - 财政年份:2022
- 资助金额:
$ 4.27万 - 项目类别:
Recessive lethal alleles linked to seed abortion and their effect on fruit development in blueberries
与种子败育相关的隐性致死等位基因及其对蓝莓果实发育的影响
- 批准号:
22K05630 - 财政年份:2022
- 资助金额:
$ 4.27万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Investigating the Effect of APOE Alleles on Neuro-Immunity of Human Brain Borders in Normal Aging and Alzheimer's Disease Using Single-Cell Multi-Omics and In Vitro Organoids
使用单细胞多组学和体外类器官研究 APOE 等位基因对正常衰老和阿尔茨海默病中人脑边界神经免疫的影响
- 批准号:
10525070 - 财政年份:2022
- 资助金额:
$ 4.27万 - 项目类别:
Leveraging the Evolutionary History to Improve Identification of Trait-Associated Alleles and Risk Stratification Models in Native Hawaiians
利用进化历史来改进夏威夷原住民性状相关等位基因的识别和风险分层模型
- 批准号:
10689017 - 财政年份:2022
- 资助金额:
$ 4.27万 - 项目类别: