Dpp-spalt信号通路调控果蝇翅形貌发生

发布时间：2017-12-26 20:05

本文关键词：Dpp-spalt信号通路调控果蝇翅形貌发生　出处：《中国农业大学》2016年博士论文　论文类型：学位论文

【摘要】：果蝇翅的成虫盘是由相对的两细胞层组成的囊状结构,这两层细胞层分别是鳞片状上皮细胞(peripodial epithelium, PE,也称围肢膜)和柱状细胞层(disc proper, DP,也被称为假复层柱状上皮细胞)。柱状细胞层细胞形貌发生的分子机制已经研究地十分深入,然而,鳞片状细胞层细胞形貌发生的机制还未得到很好的研究。前人研究中证明,在果蝇翅发育过程中,Decapentaplegic(Dpp)信号对于柱状细胞层细胞形貌发生过程中起到重要调节作用。也有报道证实Dpp信号参与调控鳞片状细胞层的正确形成,但是对于其更为详细的调节机制还知之甚少。本文中,我们通过遗传学工具操控Dpp信号通路中系列因子的表达水平,研究Dpp及其下游基因对于鳞片状细胞层细胞形貌正确发生的影响。本研究发现：(1) pMad作为Dpp信号的传导者及其信号活力指示因子在鳞片状细胞层中有表达,但是Dpp信号的靶标基因spalt (sal)和optomotor-blind (omb)只在柱状细胞层中表达,而在鳞片状细胞层中没有表达。(2)Sal蛋白在鳞片状细胞层内的缺失对于鳞片状细胞层的形成至关重要。在鳞片状细胞层异位表达sal可以导致鳞片状细胞高度增加。在柱状细胞层下调sal可以导致柱状细胞高度缩短。(3)除此之外,我们发现,已知转录调控调节因子Lines在鳞片状细胞层中异位表达时,可以将鳞片状细胞命运转化为柱状细胞,而这种转变是由sal在鳞片状细胞层异常激活而介导的。我们通过实验证明,共表达sal-RNAi和lines在很大程度上可以恢复鳞片状细胞形态。(4)通过观察微管蛋白的分布,我们发现在Lines或Sal异常表达导致细胞高度增加的鳞片状细胞中,它们在形态上接近于立方体形态的中间细胞。本研究深入探究了Dpp信号通路在果蝇翅芽鳞片状细胞层细胞形貌发生过程的重要作用,发现基因5al在此过程中起到关键调节作用,由于Sall家族在生物体中保守性较高,本研究也为相关人类疾病的研究提供了新思路。
[Abstract]:Drosophila wing's adult disk is a cystic structure composed of two cell layers. The two cell layers are peripodial epithelium, PE, also known as pericapsular membrane and columnar cell layer (disc proper, DP, also known as pseudo stratified columnar epithelial cells). The molecular mechanism of cell morphologies in columnar cell layer has been studied deeply. However, the mechanism of morphologies in squamous cell layer has not been well studied. Previous studies have demonstrated that Decapentaplegic (Dpp) signaling plays an important role in the morphogony of columnar cell layer during Drosophila wing development. There have also been reports that Dpp signals are involved in the correct formation of the squamous cell layer, but little is known about its more detailed regulatory mechanism. In this paper, we manipulate the expression of a series of factors in Dpp signaling pathway by genetic tools, and study the effect of Dpp and its downstream genes on the correct appearance of cell morphology in squamous cell layer. This study found that: (1) pMad as the Dpp signal transmission and signal energy indicator is expressed in squamous cell layer, but the target gene spalt Dpp signal (SAL) and optomotor-blind (OMB) is expressed only in the columnar cell layer, and no expression in squamous cell layer. (2) the loss of Sal protein in the squamous cell layer is crucial to the formation of the squamous cell layer. The ectopic expression of SAL in the squamous cell layer can lead to a high increase in the scale of the squamous cells. The downregulation of SAL in the columnar cell layer can lead to a height reduction of columnar cells. (3) besides, we found that the ectopic expression of Lines, a known transcription regulator, can transform squamous cell fate into columnar cells, which is mediated by Sal's abnormal activation in squamous cell layer. We have shown that the co expression of sal-RNAi and lines can greatly restore the morphology of the squamous cell cells. (4) by observing the distribution of tubulin, we found that abnormal expression of Lines or Sal resulted in highly increased squamous cells, which were similar to cubic cells in morphology. This study explored the Dpp signaling pathway plays an important role in the Drosophila wing bud squama cell morphology process, play a key regulatory role that 5Al gene in this process, the family of Sall in the organism is relatively conservative, this study provides a new way for study of relevant human diseases.
【学位授予单位】：中国农业大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：Q34

【相似文献】