Body size control genes & TGF-beta signaling C. elegans

超出提供的空间。转化生长因子β(TGFbeta)相关配体调节细胞分化和功能的许多方面，信号通路的组成部分在人类癌症中扮演肿瘤抑制因子的角色。在线虫中，与转化生长因子β相关的信号通路DBL-1控制着身体大小和雄性尾巴的形态发生。对这一途径的研究已经在识别保守的信号成分方面取得了丰硕的成果，包括Smad信号转导分子SMA-2、SMA-3和SMA-4。Smad蛋白是一种细胞质成分，受激活的TGFβ受体直接调节，转位到细胞核并产生转录反应。鉴于转化生长因子β反应的多样性和细胞类型特异性，这种简单的Smad信号机制必须需要其他信号成分的调节。为了确定DBL-1途径的其他成分，特别是那些赋予特定途径反应的成分，进行了影响身体大小的额外突变的正向遗传筛查。这一筛选确定了几个新的基因，包括SMA-20。对SMA-20突变表型的初步分析表明，它在DBL-1信号转导中起着空间和时间上的特异性作用。为了研究SMA-20在体型调节、雄性尾巴发育和转化生长因子β相关信号转导中的作用，我们建议使用SMA-20的遗传、分子和表型分析。我们的目标是(1)确定SMA-20完全丧失功能(空)的表型；(2)定位和克隆SMA-20；以及(3)分析SMA-20的细胞和时间作用焦点。这些实验将为纽约大学皇后学院的一名研究生和一名或多名本科生提供教育和科学培训机会。由于转化生长因子β超家族配体、它们的受体、Smads和SchNurri都是通过遥远的动物门保守的，因此研究遗传上易驯化的模式生物中的新成分应该有助于深入了解它们在其他生物中的功能。表演网站========================================Section End===========================================

EXCEED THE SPACE PROVIDED. Transforming growth factor beta (TGFbeta) related ligands regulate many aspects of cell differentiation and function, and components of the signaling pathway act as tumor suppressors involved in human cancers. In the nematode C. elegans, a TGFbeta-related signaling pathway, the dbl-1 pathway, controls body size and male tail morphogenesis. Studies of this pathway have previously been fruitful in identifying conserved signaling components, including the Smad signal transducers SMA-2, SMA-3, and SMA-4. Smad proteins are cytoplasmic components that are directly regulated by activated TGFbeta receptors to translocate into the nucleus and generate transcriptional responses. Given the diversity and cell type specificity of TGFbeta responses, this simple Smad signaling mechanism must require modulation by other signaling components. To identify additional components of the dbl-1 pathway and in particular those that confer specific pathway responses, a forward genetic screen for additional mutations affecting body size was performed. This screen identified several new genes, including sma-20. Preliminary analysis of sma-20 mutant phenotypes suggests that it plays spatially and temporally specific roles in dbl-1 signaling. To characterize the roles of sma-20 in body size regulation, male tail development, and TGFbeta-related signal transduction, we propose to use genetic, molecular, and phenotypic analyses of sma-20. Our goals are to (1) determine the complete loss of function (null) phenotype of sma-20; (2) map and positionally clone sma-20; and (3) analyze sma-20 cellular and temporal focus of action. These experiments will provide educational and scientific training opportunities for a graduate student and one or more undergraduate students at Queens College, CUNY. Since TGFbeta superfamily ligands, their receptors, the Smads, and Schnurri are all conserved through distant animal phyla, studying new components in a genetically tractable model organism should provide insight into their functions in other organisms as well. PERFORMANCE SITE ========================================Section End===========================================