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

ABSTRACT__________________________________________________________________________________ 上皮组织排列在多细胞生物体的器官、血管和腔内以提供保护， 调节化学交换，为底层组织分泌荷尔蒙。上皮细胞之间的转化 维持正常细胞功能的立方、柱状和鳞状形态，以及不适当的改变 可能导致许多疾病，包括颈动脉疾病、亨廷顿氏病和肿瘤 恶毒。果蝇卵泡上皮覆盖着发育中的卵室，提供了一种 这是了解发育信号如何控制上皮细胞变化的极佳模型。滤泡的一个子集 细胞经历了戏剧性的扁平化过程，从长方体变成鳞状。虽然研究表明 发现了可以改变细胞形状的分子，这种分子在扁平化过程中尤其重要，即基因控制 这一动态和复杂的鳞状细胞(SC)过程仍不清楚。我们发现锌指 卵泡上皮中的转录因子BRoad(BR)需要将后卵泡细胞从 卵子发生早期为长方体到柱状。我们还发现，抑制BR在中期的表达。 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。 这与蜕皮激素在其他组织中积极调节BR表达的已知能力形成了鲜明对比。我们现在 建议研究果蝇中BR表达负调控的机制 卵子发生，目的是了解BR驱动的上皮重塑是如何被控制的。我们假设 蜕皮激素和JAK/STAT通路对共同的下游靶BR TO产生负面作用 调控这种戏剧性形态变化的时间和位置。为了检验我们的假设，我们将 首先研究蜕皮激素和JAK/STAT信号在BR介导的SC伸展中的作用(目标1)；然后 研究参与BR介导的SC伸展的下游分子(目标2)。我们的发现将提供 全面了解SC形态发生所涉及的分子和形态步骤， 为上皮性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.