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

摘要_ 上皮组织排列在多细胞生物的器官、血管和腔中以提供保护， 调节化学交换，并为底层组织分泌激素。上皮细胞之间的过渡 立方、柱状和鳞状形态，以维持正常的细胞功能，以及不适当的变化 可能导致许多疾病，包括颈动脉疾病、亨廷顿病和肿瘤 恶性肿瘤果蝇滤泡上皮覆盖着发育中的卵室， 这是了解发育信号如何控制上皮变化的极好模型。滤泡细胞亚群 细胞经历了一个戏剧性的扁平化过程，从长方体变成鳞状。虽然研究 揭示了可以改变细胞形状的分子，这些分子在扁平化中特别重要，扁平化是遗传控制的一个方面。 这种动态和复杂的鳞状细胞（SC）过程仍不清楚。我们发现锌指 滤泡上皮中的转录因子Broad（Br）是将后滤泡细胞从 在卵子发生早期立方形到柱状。我们还发现，抑制中- 通过蜕皮激素和JAK/STAT信号通路的卵子发生调节立方-鳞状形状的变化。 这与蜕皮激素已知的在其他组织中正调节Br表达的能力形成对比。我们现在 建议研究Br表达在果蝇中负调控的机制， 卵子发生的目的是了解如何控制溴驱动的上皮重塑。我们假设 蜕皮激素和JAK/STAT途径对共同的下游靶点Br起负作用， 调节这种戏剧性形态变化的时间和位置。为了验证我们的假设，我们将 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（Aim 1）;然后 研究参与Br介导的SC拉伸的下游分子（目的2）。我们的发现将提供 全面了解SC形态发生中涉及的分子和形态学步骤， 为上皮疾病的病因提供了新的线索。

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.