Coordination of growth and patterning during development

描述(由申请人提供)：本提案的总体目标是了解在发育过程中连接细胞生长、细胞分裂和细胞命运模式的分子机制。动物的生长是这些不同过程的精确协调的结果，也是单个器官和组织内相邻细胞之间复杂相互作用的结果。尽管控制细胞增殖、细胞生物合成和细胞命运的分子途径已知，但尚不清楚的是它们在组织和器官的发育过程中如何相互交叉和相互影响。为此，我们建议进行体内研究，以果蝇翅膀为模型系统，确定将生长与图案形成联系起来的机制。这项提议有三个主要目标。首先，我们将确定Wingless是模式调节基因家族中保守的成员之一，它如何指导发育中的翅膀的生长。这些研究将确定Wingless用于控制体内细胞生长、细胞周期进展和细胞存活的生长调控靶点和机制。其次，我们将使用一系列遗传和分子分析来了解调节器官大小的内在遗传程序。我们的实验将讨论发育中的器官如何监测它们的质量，细胞如何感知它们之间的生长速度差异，哪些生长参数对生长变化做出反应，并确定这些功能如何相互作用来控制翅膀的大小和形状。第三，为了确定生长和模式之间的联系，我们将进行基因筛查，以识别在不改变模式的情况下促进细胞自主生长的基因。多年来，果蝇一直是一个开创性的遗传模型系统，我们的研究为有力地分析细胞、器官和动物生长的基本分子联系提供了机会。这些研究与理解人类发育过程中的生长密切相关，因此，可能会导致促进组织再生和移植的新疗法，以及预防癌症等病理性生长疾病的疗法。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to understand the molecular mechanisms that link cell growth, cell division, and cell fate patterning during development. Animal growth results from the precise coordination of these different processes, as well as from complex interactions between neighboring cells within individual organs and tissues. Although the molecular pathways that control cell proliferation, cellular biosynthesis, and cell fate specification are known, what remains unclear is how they intersect and are influenced by each other during the development of tissues and organs. To this end, we propose in vivo studies to determine the mechanisms that link growth to pattern formation, using the Drosophila wing as a model system. This proposal has three major goals. First, we will determine how Wingless, a member of the conserved Wnt gene family of pattern regulators, directs growth of the developing wing. These studies will identify the growth regulatory targets and mechanisms used by Wingless to control cellular growth, cell cycle progression, and cell survival in vivo. Second, we will use a series of genetic and molecular assays to understand the intrinsic genetic program that regulates organ size. Our experiments will address how developing organs monitor their mass, how cells sense growth rate differences between themselves, which growth parameters respond to growth alterations, and determine how these features interact to control wing size and shape. Third, to determine the connections between growth and patterning we will carry out a genetic screen to identify genes that promote cell autonomous growth without altering pattern. Drosophila has been a pioneering genetic model system for many years, and our studies provide an opportunity for a powerful analysis of the fundamental molecular linkages underlying cell, organ, and animal growth. These studies are germane to an understanding of growth during human development, and as such, may lead to new therapies to promote tissue regeneration and transplantation, a well as those to prevent diseases of pathological growth such as cancer.