GENETIC CONTROL OF ANIMAL DEVELOPMENT

这项工作的广泛目标是以线虫为模型，了解细胞分裂和分化的时间控制的遗传和分子机制。将进行遗传和分子分析，以确定异时性基因的调控途径如何控制线虫幼虫不同发育事件的时间协调表达。重点将放在了解某些一般的时间控制基因如何指定不同细胞类型中事件的时间，以及其他基因如何响应这些调节因子来执行特定的发育和细胞周期程序。基因筛查将被用来识别这一途径中的新基因。将对关键基因进行分子分析，以确定其产物的结构和表达，以及它们如何与其他异时基因的产物相互作用。马赛克分析将被用来评估这些基因在细胞-细胞信号过程中的作用，这些信号过程协调不同细胞系中的发育程序。重点是了解LIN-14和LIN-28的分子机制，这两个基因在了解LIN-14和LIN-28的分子机制方面发挥核心作用，LIN-14和LIN-28在控制不同的幼虫细胞谱系方面发挥核心作用。此外，主要的努力将集中在了解异时性基因如何控制细胞周期和外阴前体细胞的发育能力。一般而言，线虫的异时性基因为研究控制细胞分裂和分化的遗传和分子机制提供了机会，这些机制是所有多细胞发育的核心过程。更具体地说，异时基因影响发育计时的事实提供了一个独特的系统，在这个系统中详细研究了时间控制的调节机制。

The broad goal of this work is to understand the genetic and molecular mechanisms of the temporal control of cell division and differentiation using the nematode C. elegans as a model. Genetic and molecular analysis will be performed to determine how the regulatory pathway of heterochronic genes controls the temporally coordinated expression of diverse developmental events in C. elegans larvae. Emphasis will be placed on understanding how certain general temporal control genes specify the timing of events in diverse cell types and how other genes respond to these regulators to execute particular developmental and cell cycle programs. Genetic screens will be employed to identify new genes in this pathway. Key genes will be analyzed molecularly to determine the structure and expression of their products, and how they interact with the products of other heterochronic genes. Mosaic analysis will be used to assess the role of these genes in cell-cell signaling processes that coordinate developmental programs in separate cell lineages. Emphasis will be placed on understanding the molecular mechanism of how lin-14 and lin-28, genes that play central roles in the control of understanding the molecular mechanism of how lin-14 and lin-28, genes that play central roles in the control of diverse larval cell lineages., are regulated by the novel regulatory molecule encoded by lin-4. Also, a major effort will be focused on understanding how the heterochronic genes control cell cycle and developmental competence of vulval precursor cells. Generally speaking, the C. elegans heterochronic genes offer an opportunity to study the genetic and molecular mechanisms controlling cell division and differentiation, processes central to all multi-cellular development. More specifically, the fact that the heterochronic genes affect developmental timing provides a unique system in which to examine in detail the regulatory mechanisms underlying temporal control.