A Hox-Wnt-Sox signaling axis regulates lung development, patterning and branching

Hox-Wnt-Sox 信号轴调节肺发育、模式和分支

• 批准号: 8557787
• 负责人: Jason Spence
• 金额: $ 37.01万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8557787
• 关键词: Affect; Area; Bronchi; Chemicals; Complex; Congenital Abnormality; Data; Defect; Disease; Distal; Embryonic Development; Epithelial; Epithelium; Event; Genes; Genetic; Goals; Human; In Vitro; Inherited; Laboratories; Lead; Ligands; Link; Lung; Maintenance; Mediating; Mesenchymal; Mesenchyme; Molecular; Molecular Genetics; Morphogenesis; Mus; Mutation; Neonatal; Organogenesis; Pathway interactions; Pattern; Phenotype; Play; Process; Regulation; Respiratory System; Respiratory distress; Role; Signal Pathway; Signal Transduction; Testing; Time; Trachea; Work; base; body system; design; in vivo; injury and repair; insight; intercellular communication; loss of function; lung development; mutant; novel; public health relevance; research study; spatiotemporal; transcription factor

DESCRIPTION (provided by applicant): This proposal is based on two novel findings that identify both Sox9 and Hox5 as critical players in lung development. In addition to identifying novel roles for these transcription factors in early lung patterning and branching morphogenesis, our preliminary evidence suggests that Hox5 regulates Wnt signaling in the mesenchyme to control mesenchyme-epithelial crosstalk upstream of Sox9 expression in both the mesenchyme and epithelium. By identifying novel molecular mechanisms by which Hox5 and Sox9 regulate lung development, the proposed work will add significant new data to our existing understanding of lung organogenesis. Furthermore, the proposed experiments are designed to synthesize a comprehensive view of how Sox9 and Hox5 integrate with the Wnt/¿-catenin signaling pathway to regulate early events in lung development, including patterning, branching morphogenesis, proliferation and differentiation. In order to fully elucidate this novel Hox-Wnt-Sox signaling axi, we will define Hox5- and Sox9-mediated molecular regulation of lung development and determine the mechanisms by which Hox5 modulates Wnt/¿-catenin signaling to control mesenchymal-epithelial crosstalk and Sox9 expression.

描述（由申请人提供）：该提案基于两项新发现，确定Sox 9和Hox 5是肺发育的关键参与者。除了确定这些转录因子在早期肺模式和分支形态发生中的新作用外，我们的初步证据表明，Hox 5调节间充质中的Wnt信号传导，以控制间充质和上皮中Sox 9表达上游的间充质-上皮串扰。通过确定Hox 5和Sox 9调节肺发育的新分子机制，拟议的工作将为我们现有的肺器官发生的理解增加重要的新数据。此外，拟议的实验旨在全面了解Sox 9和Hox 5如何与Wnt/â-连环蛋白信号通路整合，以调节肺发育的早期事件，包括模式化、分支形态发生、增殖和分化。为了充分阐明这种新的Hox-Wnt-Sox信号转导轴，我们将定义Hox 5和Sox 9介导的肺发育的分子调节，并确定Hox 5调节Wnt/<$-连环蛋白信号转导以控制间充质-上皮串扰和Sox 9表达的机制。