rOLE OF TRACHEALESS IN EMBRYONIC TUBE FORMATION

无气管在胚胎管形成中的作用

• 批准号: 6150541
• 负责人: Deborah J Andrew
• 金额: $ 20.54万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6150541
• 关键词: DNA binding protein; Drosophilidae; alternatives to animals in research; antibody; cell adhesion; cell population study; developmental genetics; embryo /fetus; embryogenesis; gene expression; genetic regulation; morphology; mutant; phenotype; salivary glands; trachea; transcription factor

Salivary gland formation in the developing Drosophila embryo provides a excellent system for understanding the molecular and cellular interactions required for tissue morphogenesis. Salivary gland cells participate in many of the movements characteristic of tissue differentiation, including nuclear repositioning, cell shape changes, invagination and tube formation. Only two major cell types comprise the Drosophila specialized for secretion, and the salivary duct cells, which are squamous epithelial cells organized into a polarized epithelium specialized for the passage of secretions. Once cells are specified to become salivary gland, they differentiate without further cell division; growth occurs simply by increasing the volume of individual cells. Many of the genes that control salivary gland fate determination and early morphogenesis have been identified and characterized. In previous work, we identified trachea-less (trh), a gene encoding a transcription factor required for tube formation in the salivary gland duct, trachea and filzkorper. In trh mutant embryos, each of these group of cells fails to invaginate to form their characteristic tubes. We have shown that trh is expressed in these tube-forming cells and have identified the molecules that control trh expression in the salivary gland duct. The goal of the research proposed here is to understand how the TRH transcription factor controls tube formation not only in the salivary duct but in other cells that also depend on its activity. We will first describe the cellular changes that occur during normal tube formation as a basis for assessing the relative contribution of trh and its downstream target genes in forming the tubes of the salivary duct and trachea. Second, we will identify these downstream genes and characterize their corresponding mutant phenotypes. Finally, we will study the molecular interactions between the TRH and the genes it regulates. The proposed work will link developmental genetics to the cell biology of organ assembly.

发育中的果蝇胚胎中唾液腺的形成提供了 理解分子和细胞的优秀系统 组织形态发生所需的相互作用。唾液腺细胞 参与组织的许多运动特征 分化，包括核重新定位、细胞形状变化、 内陷和管形成。仅两种主要细胞类型组成 果蝇专门负责分泌，而唾液管细胞则负责分泌 鳞状上皮细胞组织成极化上皮 专门负责分泌物的通过。一旦单元格被指定为 成为唾液腺，它们无需进一步细胞分裂即可分化； 生长仅通过增加单个细胞的体积来实现。许多 控制唾液腺命运决定的基因和早期 形态发生已被鉴定和表征。 在之前的工作中，我们鉴定了气管少（trh），一个编码a的基因 唾液腺管形成所需的转录因子 导管、气管和 filzkorper。在 trh 突变胚胎中，每一组 的细胞无法内陷形成其特征性的管。我们有 显示 trh 在这些管形成细胞中表达并具有 鉴定出控制唾液中 trh 表达的分子 腺管。 这里提出的研究的目的是了解 TRH 如何 转录因子不仅在唾液中控制管的形成 导管，但在其他细胞中也取决于其活性。我们首先会 将正常管形成过程中发生的细胞变化描述为 评估 TRH 及其相关贡献的基础 形成唾液管的下游靶基因 气管。其次，我们将识别这些下游基因并 表征其相应的突变表型。最后，我们将 研究 TRH 与其基因之间的分子相互作用 调节。拟议的工作将把发育遗传学与 器官组装的细胞生物学。