Developmental regulation of epithelial cell

上皮细胞的发育调控

• 批准号: 10938764
• 负责人: Dongyu Jia
• 金额: $ 44.76万
• 依托单位: KENNESAW STATE 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 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10938764
• 关键词: Developmental; regulation; epithelial; cell

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_____ 上皮组织在多细胞生物的器官，血管和空腔中饰有保护，以提供保护， 调节化学交换，并为基础组织分泌骑马。上皮细胞过渡 立方体，柱状和鳞状形态，以维持正常的细胞功能，并且变化不当 可能导致许多疾病，包括颈动脉疾病，亨廷顿氏病和肿瘤 恶性。覆盖发育中的卵室的果蝇卵泡上皮提供了 理解开发信号如何控制上皮变化的绝佳模型。卵泡的子集 细胞经历了一个戏剧性的扁平化过程，从长方体变为鳞状。而研究有 揭示的分子可以改变细胞形状，并且在扁平化中尤其重要， 这个动态且复杂的鳞状细胞（SC）过程尚不清楚。我们发现锌指 从卵泡上皮中的转录因子宽（BR）是从后卵形细胞过渡的卵泡上皮细胞需要的 在卵子发生早期的立方体到柱状形状。我们还发现，中期中BR表达的抑制 Ecdysone和Jak/Stat信号通路的卵子发生调节立方体形状的变化。 这与ecdysone的已知能力相反，可以正调节其他组织中的BR表达。我们现在 提议检查果蝇期间BR表达受负调控的机制 卵子发生的目的是了解如何控制BR驱动的上皮重塑。我们假设 Ecdysone和Jak/Stat途径对公共下游目标BR负有负面作用 调节这种戏剧性形态学变化的时间和位置。为了检验我们的假设，我们将 首先研究Ecdysone和Jak/Stat信号在BR介导的SC拉伸中的作用（AIM 1）；然后 研究与BR介导的SC拉伸有关的下游分子（AIM 2）。我们的发现将提供 对SC形态发生涉及的分子和形态步骤的全面理解， 为上皮疾病的原因散发出新的灯光。