Genetic Control of Animal Development

描述(申请人提供)：这项工作的广泛目标是了解在动物发育过程中控制细胞分裂和分化的遗传和分子机制。我们将主要使用线虫作为模型系统。将对线虫异时性基因进行遗传和分子分析，以确定这一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。将进行遗传和生化实验，以探索在控制不同幼虫细胞谱系中发挥核心作用的LIN-14和LIN-28基因如何受LIN-4和LET-7家族基因的microRNA产物转录后调控的分子机制。在线虫中，除了lin-4和let-7之外，至少还有100个不同的microRNA基因，这些基因的功能在很大程度上是未知的。我们将使用分子和计算方法来识别额外的microRNA基因及其调控靶标，并将使用遗传学方法来确定所有线虫microRNA基因的生物学功能。线虫是一个很好的微RNA功能遗传分析系统，由于许多线虫的microRNAs在哺乳动物中是保守的，了解它们在线虫中的作用将有助于了解基于microRNA的调节电路对人类健康的意义。

DESCRIPTION (provided by applicant): The broad goal of this work is to understand the genetic and molecular mechanisms of the control of cell division and differentiation during animal development. We will chiefly use C. elegans as a model system. Genetic and molecular analysis of C. elegans heterochronic genes will be performed to determine how this regulatory pathway controls the temporally coordinated expression of diverse developmental events in C. elegans larvae. Genetic and biochemical experiments will be performed to explore the molecular mechanisms of how lin-14 and lin-28, genes that play central roles in the control of diverse larval cell lineages, are regulated post-transcriptionally by the microRNA products of the lin-4 and let-7 family genes. There are at least 100 distinct microRNA genes in C. elegans, besides lin-4 and let-7, and the functions of these are largely unknown. We will use molecular and computational approaches to identify additional microRNA genes, and their regulatory targets, and we will employ genetic methods to determine the biological functions of all the C. elegans microRNA genes. C. elegans is an excellent system for the genetic analysis of microRNA function, and since many of the C. elegans microRNAs are conserved in mammals, understanding their roles in C. elegans should inform about the human health significance of microRNA-based regulatory circuits.