Early Developmental Gene Regulation in Dictyostelium

真核生物的正常发育需要大量具有精确时间和组织选择性的基因的差异表达。辛格尔顿博士正在利用细胞黏菌盘状盘基骨菌的发育程序，作为一个系统来研究差异基因表达的分子细节和这种表达的发育调节。他已经确定并描述了三组基因，这些基因在发育开始或之后不久表现出各种形式的差异表达。两组在发育开始时失活，失活事件的机制在两组之间有很大不同。第三组基因在发育开始时被诱导，并在程序的最初几个小时内短暂表达。辛格尔顿博士对无法发育的突变菌株的分析，将这些基因细分为那些似乎处于同一调控体系下的基因。他将继续分离出与这些基因相对应的基因组克隆，并利用它们来研究与这些基因调控有关的分子事件。转录和适当调控所需的序列将被定义，介导调控事件的蛋白质因子将被识别和表征。一个系统产生和识别突变存在于编码调控机制的基因将被开发。最后，通过诱变一个选定的基因，他将开始讨论这些基因在发育程序的建立中所起的作用。这些调查应该产生一个更全面的复杂性和细节的监管事件，导致激活和建立使用一个简单的模型系统的发展。它们将为早期发育控制过程中使用的分子机制提供重要的见解。

Proper development of eukaryotic organisms requires differential expression of a multitude of genes with precise timing and tissue selectivity. Dr. Singleton is utilizing the developmental program of the cellular slime mold, Dictyostelium discoideum, as a system to investigate the molecular details of differential gene expression and the developmental regulation of this expression. He has identified and characterized three groups of genes which show various forms of differential expression upon the onset of development or shortly thereafter. Two groups are deactivated upon initiation of development, and the mechanisms of the deactivation events are very different between the two groups. A third set of genes is induced as development begins and is transiently expressed during the first few hours of the program. Dr. Singleton's analysis of mutant strains unable to develop has led to subclassification of the genes into those that appear to be under the same regulatory system. He will continue to isolate the genomic clones corresponding to certain of these genes and utilize them to investigate the molecular events involved in their regulation. The sequences necessary for transcription and proper regulation will be defined, and the protein factors which mediate the regulatory events will be identified and characterized. A system for generating and identifying mutations present in the genes encoding the regulatory machinery will be developed. Finally, through mutagenesis of a selected gene, he will begin to address what role these genes play in the establishment of the developmental program. %%% These investigations should result in a more comprehensive picture of the complexity and the details of the regulatory events leading to the activation and establishment of development using a simple model system. They will provide significant insight into the molecular machinery that is utilized in the control processes of early development.