Cell type divergence in Dictyostelium - delineation of the signalling pathway that leads to prespore cell differentiatio

盘基网柄菌的细胞类型分化 - 导致前孢子细胞分化的信号通路的描述

• 批准号: G0600244/1
• 负责人: Jeffrey Williams
• 金额: $ 33.4万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600244%2F1
• 关键词: Cell; type; divergence; Dictyostelium; delineation

Animals and plants are built up of millions of individual cells that can be classified into many hundreds of different cell types by their form and function. The cell types differ in these two fundamental properties because each kind of cell reads out a different sub-set of the messages that are written within the gene set of that particular organism. The process whereby cells diverge from one another, in the sub-set of messages that they express as proteins, is called differentiation. Improper differentiation leads to many kinds of human diseases, e.g. developmental abnormalities in embryos and cancer in children and adults. Studying differentiation as it occurs in a mammalian embryo is difficult, because so many cell types are being simultaneously generated, they are often not easily accessible and certain kinds of genetic analysis are not possible.Therefore, developmental biologists have found it immensely valuable to study simpler, ?model? organisms such as the fruit fly. The simplest model organism to display a choice of cell fate is the soil-living amoeba Dictyostelium. In just 24 hours, Dictyostelium cells aggregate together and differentiate as either stalk cells or spore cells. At an intermediate stage of development, the slug stage, the stalk and spore cell precursors are arranged in a linear array along the slug, where they can be analysed and manipulated. Prestalk cells occupy the front one-fifth of the slug and prespore cells occupy the rear four-fifths. Genes are ?read? when proteins, known as transcription factors, recognise specific signal sequences in the DNA adjacent to the gene. The Dictyostelium transcription factors that direct the reading of genes necessary to differentiate as a prestalk cell are partially characterised. However, the transcription factors that direct reading of the genes necessary to become a prespore cell are unknown. The aim of this project is to identify such factors. Although it has a somewhat different mode of development to that of plants and animals, the genome sequence of Dictyostelium show that it shares many gene products with them. Therefore, genes and genetic pathways discovered in Dictyostelium are often relevant to higher organisms and to the diseases that beset them.

动物和植物是由数百万个细胞组成的，这些细胞可以根据它们的形式和功能分为数百种不同的细胞类型。细胞类型在这两个基本特性上是不同的，因为每种细胞都读出了写在特定生物体基因组中的不同信息子集。细胞在它们表达为蛋白质的信息子集中彼此分化的过程被称为分化。分化不当会导致多种人类疾病，例如胚胎发育异常以及儿童和成人癌症。研究哺乳动物胚胎中的分化是困难的，因为许多细胞类型同时产生，它们通常不容易获得，某些类型的遗传分析是不可能的。模特儿？像果蝇这样的生物。显示细胞命运选择的最简单的模式生物是生活在土壤中的变形虫Dictyosteoba。在短短24小时内，网骨藻细胞聚集在一起并分化为柄细胞或孢子细胞。在发育的中间阶段，蛞蝓阶段，柄和孢子细胞前体沿着蛞蝓以线性阵列沿着排列，在那里它们可以被分析和操纵。前柄细胞占蛞蝓体前部的五分之一，前孢子细胞占后部的五分之四。基因是？阅读？当被称为转录因子的蛋白质识别与基因相邻的DNA中的特定信号序列时。指导阅读分化为前柄细胞所必需的基因的网骨藻转录因子的部分特征。然而，指导阅读成为前孢子细胞所必需的基因的转录因子是未知的。本项目的目的是确定这些因素。虽然它与植物和动物的发育模式有所不同，但其基因组序列显示它与植物和动物有许多共同的基因产物。因此，在网骨藻中发现的基因和遗传途径通常与高等生物和困扰它们的疾病有关。