Development and function in mucociliary epithelia

粘液纤毛上皮的发育和功能

• 批准号: 9099911
• 负责人: John B Wallingford
• 金额: $ 38.63万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2018-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9099911
• 关键词: Air; Animal Model; Animals; Apical; Architecture; Asthma; Automobile Driving; Bioinformatics; Biological; Biological Models; Biological Process; Biology; Blood; Breathing; Carbon Dioxide; Cells; Cellular biology; Chronic Obstructive Airway Disease; Cilia; Computational Biology; Data; Defect; Development; Disease; Epithelial; Epithelium; Excision; Gases; Gene Expression; Gene Targeting; Genes; Genetic; Genomics; Germ; Goals; Health; Homeostasis; Image; Lead; Life; Link; Lung diseases; Mammals; Mesenchymal Stem Cells; Modeling; Morphogenesis; Mucous body substance; Oxygen; Patients; Population; Positioning Attribute; Process; RFX regulatory factor; Role; Speed; Structure; Surface; System; Time; Tissues; Transgenic Organisms; cell behavior; cell type; cilium biogenesis; fascinate; fly; genetic manipulation; imaging platform; improved; in vivo; in vivo Model; in vivo imaging; lung development; lung repair; movie; novel; novel strategies; particle; progenitor; regenerative therapy; repaired; research study; tool; transcription factor; transcriptome sequencing

DESCRIPTION (provided by applicant): The mucociliary epithelium holds a central position in both normal and pathological airway biology, as it provides both the interface for air exchange and the first line of defense against inhaled agents. Here, we will study the transcription factor RFX2, which we have shown is essential for two crucial aspects of mucociliary epithelial development and maturation. 1) Our preliminary data demonstrate an essential role for RFX2 in motile ciliogenesis. We will combine a novel model system, in vivo imaging, and a unique suite of genomic and bioinformatic approaches to study the role of RFX2 in the multi-ciliated cells. 2) Newly-born multi-ciliated cells arise from basally-located mesenchymal stem cells that must migrate apically and insert into the epithelium. This crucial process in mucociliary biology remains almost totally undefined, but we find that RFX2 is essential for this insertion. We will again combine genomics, bioinformatics and in vivo imaging to study the role of RFX2 in this context. By rapidly determining the functions of several new genes involved in distinct processes in mucociliary epithelial development, the aims in this project will provide critical new depth to our understanding of these essential tissues. Moreover, by linking a single transcription factor to the control of two such disparate aspects of mucociliary epithelial biology, the experiments here will add crucial new breadth to our understanding as well. Impact: Experiments proposed here will lead to a more detailed understanding of the cell biology and genetics of mucociliary epithelia. The results will aid in the development of regenerative therapies aimed at repairing or restoring damaged tissue and improving mucus clearance in patients with airway disease.

描述（由申请人提供）：粘纤毛上皮在正常和病理气道生物学中都处于中心位置，因为它既提供了空气交换的接口，又提供针对吸入剂的第一道防线。在这里，我们将研究转录因子RFX2，我们已经证明这对于粘膜上皮发育和成熟的两个关键方面至关重要。 1）我们的初步数据证明了RFX2在运动纤毛发生中的重要作用。我们将结合一种新型的模型系统，体内成像，以及一个独特的基因组和生物信息学方法，以研究RFX2在多丝纤维细胞中的作用。 2）新生出生的多细胞细胞是由基本的间充质干细胞产生的，这些干细胞必须迁移并插入上皮。粘膜生物学的关键过程几乎完全不确定，但是我们发现RFX2对于此插入至关重要。我们将再次将基因组学，生物信息学和体内成像结合起来，以研究RFX2在这种情况下的作用。通过快速确定粘膜上皮开发中不同过程中几个新基因的功能，该项目的目标将提供关键的新新 深入了解我们对这些基本组织的理解。此外，通过将单个转录因子与粘膜上皮生物学的两个不同方面的控制联系起来，此处的实验也将为我们的理解增加至关重要的新广度。影响：此处提出的实验将导致对粘膜上皮细胞生物学和遗传学的更详细的了解。结果将有助于开发旨在修复或恢复受损组织并改善气道疾病患者粘液清除的再生疗法。