Mechanisms of early tracheal specification and morphogenesis
早期气管规格和形态发生的机制
基本信息
- 批准号:10369014
- 负责人:
- 金额:$ 40.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-06 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:ActomyosinAffectAutomobile DrivingBiologicalCell Culture TechniquesCellsChIP-seqChickCoupledCuesData SetDevelopmentDevelopmental ProcessDiseaseDorsalEmbryoEndodermEph Family ReceptorsEphrin-B2EsophagusEventFailureFutureGastrointestinal tract structureGene ExpressionGene Expression ProfileGenesGeneticIndividualKnowledgeLinkLive BirthLungMaintenanceMethodsMolecularMorphogenesisMosaicismMusPathway interactionsPatternPluripotent Stem CellsPrimitive foregut structureProcessRNA immunoprecipitation sequencingReceptor Protein-Tyrosine KinasesRegenerative engineeringRegulationRegulator GenesRepressionResourcesRespiratory SystemSignal TransductionSpecific qualifier valueStructureTissue EngineeringTissuesTo specifyTracheaTracheoesophageal FistulaTubeWorkXenopuscell fate specificationconfocal imagingcongenital anomalyexperimental studygene regulatory networkgenetic approachgenome-widehuman diseaseimaging approachimprovedin vivo evaluationinsightmouse geneticsmouse modelmutantphysical separationregenerative biologyrespiratorytranscription factortranscriptome sequencing
项目摘要
Project summary
Congenital anomalies of the trachea, including tracheoesophageal fistula (TEF), are common, affecting around
1:3000 live births. TEF is defined as the inappropriate maintenance of a connection between the trachea and
esophagus, and arises as a result of a failure of the complete separation of these structures from their common
origin, the foregut endoderm tube. Normally, induction of respiratory identity in the ventral foregut endoderm
and initiation of lung bud outgrowth is followed immediately by a morphogenetic separation of the ventral
trachea from the dorsal esophagus. Despite the common occurrence of TEF, our understanding of the
pathways that control this developmental process is incomplete, and almost no knowledge exists regarding the
molecular effectors of separation. Further, the cell biological mechanisms by which the trachea separates from
the esophagus are currently not known. Our proposal incorporates genome-wide approaches including RNA
sequencing and chromatin immunoprecipitation sequencing, and integrates them with mouse genetics and
imaging approaches to better understand how control of tracheal cell fate specification is coupled to the cell
biological drivers of separation. This work will provide new insights into how early tracheal development is
regulated, improve our understanding of TEF, and provide a resource for future regenerative and tissue
engineering approaches that require a detailed understanding of early tracheal gene regulatory networks.
项目摘要
先天性气管异常,包括气管食管瘘(TEF),是常见的,影响周围
1:3000活产婴儿。TEF被定义为气管和气管之间连接的不适当维护,
食管,并作为这些结构与其共同的完全分离失败的结果而出现
起源,前肠内胚层管。通常,在腹侧前肠内胚层中诱导呼吸特性
肺芽生长开始后,腹侧的形态发生立即分离,
气管从背侧食道。尽管TEF经常发生,但我们对
控制这一发展过程的途径是不完整的,几乎没有知识存在,
分离的分子效应器。此外,气管与血管分离的细胞生物学机制也是已知的。
食道目前还不清楚。我们的建议结合了包括RNA在内的全基因组方法
测序和染色质免疫沉淀测序,并将其与小鼠遗传学和
成像方法,以更好地了解如何控制气管细胞命运的规范是耦合到细胞
分离的生物驱动力。这项工作将为早期气管发育提供新的见解
调节,提高我们对TEF的理解,并为未来的再生和组织提供资源。
需要详细了解早期气管基因调控网络的工程方法。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Delineating the early transcriptional specification of the mammalian trachea and esophagus
- DOI:10.7554/elife.55526
- 发表时间:2020-06-09
- 期刊:
- 影响因子:7.7
- 作者:Kuwahara, Akela;Lewis, Ace E.;Bush, Jeffrey O.
- 通讯作者:Bush, Jeffrey O.
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Jeffrey Ohmann Bush其他文献
Jeffrey Ohmann Bush的其他文献
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{{ truncateString('Jeffrey Ohmann Bush', 18)}}的其他基金
Signaling control and cellular basis of craniofacial morphogenesis and congenital disease
颅面形态发生和先天性疾病的信号控制和细胞基础
- 批准号:
10599976 - 财政年份:2022
- 资助金额:
$ 40.38万 - 项目类别:
Signaling control and cellular basis of craniofacial morphogenesis and congenital disease
颅面形态发生和先天性疾病的信号控制和细胞基础
- 批准号:
10447898 - 财政年份:2022
- 资助金额:
$ 40.38万 - 项目类别:
Phenotype-driven approach to understanding the function of craniofacial regulators using IMPC-generated mouse strains
使用 IMPC 产生的小鼠品系的表型驱动方法来了解颅面调节器的功能
- 批准号:
10400255 - 财政年份:2021
- 资助金额:
$ 40.38万 - 项目类别:
Mechanisms of early tracheal specification and morphogenesis
早期气管规格和形态发生的机制
- 批准号:
9888410 - 财政年份:2019
- 资助金额:
$ 40.38万 - 项目类别:
Phenotype-driven approach to understanding the function of craniofacial regulators using IMPC-generated mouse strains
使用 IMPC 产生的小鼠品系的表型驱动方法来了解颅面调节器的功能
- 批准号:
10590635 - 财政年份:2019
- 资助金额:
$ 40.38万 - 项目类别:
Phenotype-driven approach to understanding the function of craniofacial regulators using IMPC-generated mouse strains
使用 IMPC 产生的小鼠品系的表型驱动方法来了解颅面调节器的功能
- 批准号:
9765016 - 财政年份:2019
- 资助金额:
$ 40.38万 - 项目类别:
Phenotype-driven approach to understanding the function of craniofacial regulators using IMPC-generated mouse strains
使用 IMPC 产生的小鼠品系的表型驱动方法来了解颅面调节器的功能
- 批准号:
10378074 - 财政年份:2019
- 资助金额:
$ 40.38万 - 项目类别:
Phenotype-driven approach to understanding the function of craniofacial regulators using IMPC-generated mouse strains
使用 IMPC 产生的小鼠品系的表型驱动方法来了解颅面调节器的功能
- 批准号:
10806271 - 财政年份:2019
- 资助金额:
$ 40.38万 - 项目类别:
Phenotype-driven approach to understanding the function of craniofacial regulators using IMPC-generated mouse strains
使用 IMPC 产生的小鼠品系的表型驱动方法来了解颅面调节器的功能
- 批准号:
9899973 - 财政年份:2019
- 资助金额:
$ 40.38万 - 项目类别:
Phenotype-driven approach to understanding the function of craniofacial regulators using IMPC-generated mouse strains
使用 IMPC 产生的小鼠品系的表型驱动方法来了解颅面调节器的功能
- 批准号:
10589996 - 财政年份:2019
- 资助金额:
$ 40.38万 - 项目类别:
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