Developmental regulation of epithelial cell cuboidal-to-squamous transition in Drosophila follicle

果蝇滤泡上皮细胞立方体向鳞状转变的发育调控

• 批准号: 10580308
• 负责人: Dongyu Jia
• 金额: $ 4.55万
• 依托单位: GEORGIA SOUTHERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10580308
• 关键词: Adherens Junction; Anterior; Biological Models; Blood Vessels; Carotid Artery Diseases; Cell Shape; Cell physiology; Cells; Cellular Morphology; Cellular biology; Chemicals; Complex; Core Protein; Cuboidal Cell; Cuboidal Epithelium; DNA Sequence; Development; Developmental Biology; Disease; Drosophila genus; Ecdysone; Embryo; Embryonic Development; Epithelial Cells; Epithelium; Expression Profiling; Genetic; Genetic Techniques; Genetic study; Goals; Hormone secretion; Hour; Huntington Disease; Immunohistochemistry; Immunoprecipitation; Individual; Location; Maintenance; Malignant Neoplasms; Mediating; Mesenchymal; Modeling; Modification; Molecular; Molecular Biology; Morphogenesis; Morphology; Oogenesis; Organ; Organism; Ovary; Pathway interactions; Pattern; Process; Proteins; Regulation; Research; Role; Science; Shapes; Signal Pathway; Signal Transduction; Squamous Cell; Stretching; Students; Surface; System; Testing; Tissues; Training; Validation; Zinc Fingers; career; egg; experience; experimental study; improved; model organism; multidisciplinary; notch protein; novel; tissue regeneration; transcription factor; tumor; tumor progression; undergraduate student; whole genome

ABSTRACT__________________________________________________________________________________ Epithelial tissues line the organs, blood vessels, and cavities of multicellular organisms to provide protection, regulate chemical exchange, and secrete hormones for the underlying tissue. Epithelial cells transition among cuboidal, columnar, and squamous morphologies to maintain normal cellular functions, and improper changes may contribute to many diseases, including carotid artery disease, Huntington's disease, and tumor malignancy. The Drosophila follicular epithelium, which covers the developing egg chambers, provides an excellent model for understanding how developmental signals control epithelial changes. A subset of follicular cells undergoes a dramatic flattening process, changing from cuboid to squamous. While studies have revealed molecules that can modify cell shape and are especially important in flattening, the genetic control of this dynamic and complex squamous cell (SC) process remains unclear. We found that the zinc-finger transcription factor Broad (Br) in the follicular epithelium is required to transition posterior follicle cells from cuboidal to columnar shape early in oogenesis. We also discovered that suppression of Br expression in mid- oogenesis by the ecdysone and JAK/STAT signaling pathways regulates cuboidal-squamous shape changes. This contrasts with ecdysone’s known ability to positively regulate Br expression in other tissues. We now propose to examine the mechanisms by which Br expression is negatively regulated during Drosophila oogenesis with the goal of understanding how Br-driven epithelial remodeling is controlled. We hypothesize that the ecdysone and JAK/STAT pathways negatively act on a common downstream target Br to regulate the timing and location of this dramatic morphological change. To test our hypothesis, we will first investigate the roles of ecdysone and JAK/STAT signaling in Br-mediated SC stretching (Aim 1); then investigate the downstream molecules involved in Br-mediated SC stretching (Aim 2). Our findings will provide a comprehensive understanding of the molecular and morphological steps involved in SC morphogenesis, shedding new light on the causes of epithelial diseases.

抽象的_________________________________________________________________________________________________ 上皮组织排列在多细胞生物的器官、血管和腔内，提供保护， 调节化学交换，并分泌激素用于上皮细胞之间的转换。 立方体、柱状和鳞状形态以维持正常的细胞功能，以及不当的变化 可能导致许多疾病，包括颈动脉疾病、亨廷顿舞蹈病和肿瘤 果蝇滤泡上皮覆盖着正在发育的卵室，提供了一种恶性肿瘤。 用于理解发育信号如何控制上皮细胞变化的优秀模型。 研究表明，细胞经历了戏剧性的扁平化过程，从长方体变为鳞状。 揭示了可以改变细胞形状的分子，并且对于扁平化（细胞的遗传控制）特别重要 我们发现锌指这种动态且复杂的鳞状细胞（SC）过程仍不清楚。 滤泡上皮中的转录因子 Broad (Br) 需要将后滤泡细胞从 我们还发现，在卵子发生早期，Br 的表达受到抑制。 蜕皮激素和 JAK/STAT 信号通路的卵子发生调节立方鳞状形状的变化。 这与蜕皮激素在其他组织中积极调节 Br 表达的已知能力形成鲜明对比。 提议研究果蝇过程中 Br 表达受到负调控的机制 卵子发生的目的是了解如何控制 Br 驱动的上皮重塑。 蜕皮激素和 JAK/STAT 途径对共同的下游目标 Br 产生负面作用 为了检验我们的假设，我们将调节这种戏剧性形态变化的时间和位置。 首先研究蜕皮激素和 JAK/STAT 信号在 Br 介导的 SC 拉伸中的作用（目标 1）； 研究参与 Br 介导的 SC 拉伸的下游分子（目标 2）。 全面了解 SC 形态发生所涉及的分子和形态步骤， 为上皮疾病的病因提供新的线索。