Genetic Control of Animal Development

描述（由申请人提供）：这项工作的主要目标是了解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C。elegans作为一个模型系统。C.的遗传和分子分析elegans异时基因将被执行，以确定该调节途径如何控制在C.线虫幼虫将进行遗传和生物化学实验，以探索lin-14和lin-28，在不同的幼虫细胞谱系的控制中发挥核心作用的基因，是如何通过lin-4和let-7家族基因的microRNA产物进行转录后调控的分子机制。在C.除了lin-4和let-7外，elegans也是如此，并且这些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其他microRNA基因及其调控靶点，我们将采用遗传学方法来确定所有C.线虫microRNA基因。C. elegans是一个很好的microRNA功能遗传分析系统，由于许多C. elegans microRNA在哺乳动物中是保守的，了解它们在C.秀丽线虫应该了解基于微RNA的调节回路对人类健康的重要性。

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.