Coordination of growth and patterning during development

发育过程中生长和模式的协调

• 批准号: 6705017
• 负责人: Laura A Johnston
• 金额: $ 32.55万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-12 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6705017
• 关键词: Drosophilidae; apoptosis; biological signal transduction; cell cell interaction; cell differentiation; cell growth regulation; cell morphology; cell proliferation; developmental genetics; flow cytometry; genetic manipulation; genetic screening; green fluorescent proteins; histogenesis; invertebrate embryology

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.

描述（由申请人提供）：该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图案的分子机制。动物生长是由于这些不同过程的精确协调以及各个器官和组织中相邻细胞之间的复杂相互作用而产生的。尽管已知控制细胞增殖，细胞生物合成和细胞命运规范的分子途径，但尚不清楚的是它们在组织和器官的发展过程中如何相交并彼此影响。为此，我们建议使用果蝇翼作为模型系统来确定将生长与模式形成联系起来的机制。该提议有三个主要目标。首先，我们将确定无翼是模式调节剂的保守Wnt基因家族的成员如何指导发展机翼的生长。这些研究将确定无翼用于控制细胞生长，细胞周期进展和体内细胞存活的生长调节靶标和机制。其次，我们将使用一系列遗传和分子测定来了解调节器官大小的内在遗传程序。我们的实验将解决开发器官如何监测其质量，细胞如何感知生长速率之间的差异，哪些生长参数响应增长的改变，并确定这些特征如何与控制机翼的大小和形状相互作用。第三，为了确定生长与模式之间的联系，我们将执行一个遗传筛选，以识别促进细胞自主生长而不会改变模式的基因。多年来，果蝇一直是一个开创性的遗传模型系统，我们的研究为对细胞，器官和动物生长的基本分子链接的有力分析提供了机会。这些研究是对人类发展过程中生长的理解，因此可能导致新的疗法促进组织再生和移植，这是一种预防病理生长疾病（例如癌症）的疗法。