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：
Jeffrey Ohmann Bush
金额：
$ 40.38万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
https://reporter.nih.gov/project-details/10369014
关键词：
Actomyosin Affect Automobile Driving Biological Cell Culture Techniques Cells ChIP-seq Chick Coupled Cues Data Set Development Developmental Process Disease Dorsal Embryo Endoderm Eph Family Receptors Ephrin-B2 Esophagus Event Failure Future Gastrointestinal tract structure Gene Expression Gene Expression Profile Genes Genetic Individual Knowledge Link Live Birth Lung Maintenance Methods Molecular Morphogenesis Mosaicism Mus Pathway interactions Pattern Pluripotent Stem Cells Primitive foregut structure Process RNA immunoprecipitation sequencing Receptor Protein-Tyrosine Kinases Regenerative engineering Regulation Regulator Genes Repression Resources Respiratory System Signal Transduction Specific qualifier value Structure Tissue Engineering Tissues To specify Trachea Tracheoesophageal Fistula Tube Work Xenopus cell fate specification confocal imaging congenital anomaly experimental study gene regulatory network genetic approach genome-wide human disease imaging approach improved in vivo evaluation insight mouse genetics mouse model mutant physical separation regenerative biology respiratory transcription factor transcriptome 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.

项目摘要气管的先天异常，包括气管食管瘘（TEF），很常见，会影响周围 1：3000个活产。 TEF被定义为对气管之间连接的不适当维护食道，由于这些结构与共同的共同分离的失败而产生起源，前肢内胚层管。通常，腹侧内胚层诱导呼吸道身份肺芽出生的开始后立即进行腹侧形态发生分离背侧食道的气管。尽管TEF发生了常见，但我们对控制这一发展过程的途径是不完整的，几乎没有关于分离的分子效应子。此外，气管分离的细胞生物学机制食道目前尚不清楚。我们的提案结合了全基因组的方法，包括RNA 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更好地了解气管细胞命运规范的控制如何耦合到细胞分离的生物驱动力。这项工作将提供有关气管发展如何的新见解监管，提高我们对TEF的理解，并为将来再生和组织提供资源需要详细了解早期气管基因调节网络的工程方法。