Development and function in mucociliary epithelia

粘液纤毛上皮的发育和功能

• 批准号: 8714042
• 负责人: John B Wallingford
• 金额: $ 37.85万
• 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 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714042
• 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; 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; improved; in vivo; in vivo Model; in vivo imaging; lung development; lung repair; movie; novel; novel strategies; particle; progenitor; public health relevance; regenerative therapy; repaired; research study; tool; transcription factor

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）：粘膜纤毛上皮在正常和病理气道生物学中占据中心地位，因为它提供了空气交换的界面和对抗吸入剂的第一道防线。在这里，我们将研究转录因子RFX2，我们已经证明这是必不可少的两个关键方面的粘液纤毛上皮的发展和成熟。1)我们的初步数据表明RFX2在能动纤毛发生中起重要作用。我们将结合联合收割机一个新的模型系统，在体内成像，和一套独特的基因组和生物信息学的方法来研究RFX2在多纤毛细胞中的作用。2)新生的多纤毛细胞来自于位于基底的间充质干细胞，其必须向顶端迁移并插入上皮。在粘液纤毛生物学的这一关键过程仍然几乎完全不确定，但我们发现RFX2是必不可少的插入。我们将再次结合联合收割机基因组学，生物信息学和体内成像研究RFX2在这方面的作用。通过快速确定参与粘膜纤毛上皮发育不同过程的几个新基因的功能，该项目的目标将提供关键的新信息。 我们对这些重要组织的理解。此外，通过将单个转录因子与粘液纤毛上皮生物学的两个不同方面的控制联系起来，这里的实验也将为我们的理解增加至关重要的新广度。影响：这里提出的实验将导致更详细地了解粘膜纤毛上皮细胞的细胞生物学和遗传学。研究结果将有助于开发再生疗法，旨在修复或恢复受损组织并改善气道疾病患者的粘液清除。