Normal and Neoplastic Growth Regulation in the Brain

描述（由申请人提供）：此申请代表了对补充资金的请求，以支持在现有项目项目中增加新项目。项目5关注细胞周期调节因子在颗粒神经元增殖和成神经管细胞瘤细胞中的作用。马丁·f·鲁塞尔和查尔斯·L·谢尔。原计划项目的目标是增加对发育中的大脑正常和肿瘤生长的分子基础的理解。最终目的是利用这些知识来设计治疗髓母细胞瘤的新策略，髓母细胞瘤是最常见的小儿中枢神经系统恶性肿瘤。这一目标是通过四个相互作用的项目来实现的，这些项目调查不同的信号通路在中枢神经系统和脑肿瘤生长中的作用，由一个行政核心和一个生物信息学和

DESCRIPTION (provided by applicant): This application represents a request for supplemental funds to support the addition of a new project to an existing program project. Project 5 concerns the role of cell cycle regulators in granule neuron proliferation and in medulloblastoma cells from Drs. Martine F. Roussel and Charles L Sherr. The goal of the original program project is to increase understanding of the molecular basis of normal and neoplastic growth in the developing brain. The ultimate objective is to use this knowledge to devise novel strategies for treatment of medulloblastoma, the most common pediatric malignancy of the central nervous system. This objective is being pursued through four interactive projects that investigate the role of different signaling pathways in the growth of the central nervous system and brain tumors supported by an Administrative Core and a Bioinformatics and Microarray Core. In Project 1, T. Curran utilizes a mouse model of medulloblastoma to investigate the role at the Shh/Ptc/Smo pathway in tumorigenesis. This involves the use of pharmacological inhibitors in cell culture and in viva, a molecular characterization of Glil and comparison of the epigenetic and genetic alterations underlying medulloblastoma by nuclear transplant into oocytes. In Project 2, P McKinnon investigates the contribution of DNA damage signaling to medulloblastoma formation. This project is based on the characterization of a novel model for medulloblastoma in mice lacking DNA Ligase IV and p53. This analysis will involve comparison of gene expression microarray profiles of the different medulloblastomas in the program. In Project 3, R. Gilbertson is investigating the role of ERBB2 in human medulloblastoma. This involves the characterization of human medulloblastoma cell lines using pharmacological and gene expression microarray approaches. The information will be compared to the data obtained on mouse models and an existing i database of human brain tumors. A mouse model will be created in which ERBB2 is expressed in cerebellar granule neurons. In Project 4 S. Baker is studying the role of the Pten signaling pathway in growth regulation in the brain. This includes characterization of the function of downstream effector genes in the cerebellum and the creation of new mutant mouse strains to investigate its contribution to growth, proliferation an, tumorigenesis.