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.

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