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

动物和植物是由数以百万计的单个细胞组成的，这些细胞根据其形态和功能可分为数百种不同的细胞类型。不同类型的细胞在这两个基本特性上有所不同，因为每种细胞都会读出特定生物体基因集中写入的不同子集的信息。细胞在表达为蛋白质的信息子集中彼此分化的过程称为分化。分化不当导致多种人类疾病，如胚胎发育异常、儿童和成人癌症等。研究发生在哺乳动物胚胎中的分化是很困难的，因为同时产生了如此多的细胞类型，它们通常不容易获得，而且某些类型的遗传分析是不可能的。因此，发育生物学家发现，研究更简单的模型非常有价值。果蝇等生物体。表现出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盘基钢柱。在短短的24小时内，盘基骨柱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，即鼻涕虫阶段，柄和孢子细胞前体沿着鼻涕虫排列成线性阵列，在那里它们可以被分析和操纵。前柄细胞占鼻涕虫前部的五分之一，前孢子细胞占后部的五分之四。基因是被解读的。当被称为转录因子的蛋白质识别出基因附近DNA中的特定信号序列时。Dictyostelium转录因子，指导基因的阅读必要分化为前柄细胞的部分特征。然而，直接读取成为孢子前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。尽管盘齿柱菌的发育模式与植物和动物有所不同，但其基因组序列显示其与植物和动物有许多共同的基因产物。因此，在盘基ostelum中发现的基因和遗传途径往往与高等生物和困扰它们的疾病有关。

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.