Genetic Interaction Between SOX9 and RUNX2/CBFA1

SOX9 和 RUNX2/CBFA1 之间的遗传相互作用

• 批准号: 7120408
• 负责人: Guang Zhou
• 金额: $ 12.4万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120408
• 关键词: bone development; cartilage development; cell differentiation; cell growth regulation; cell line; cell morphology; chondrocytes; craniofacial; developmental genetics; embryo /fetus tissue /cell culture; gene expression; gene induction /repression; gene interaction; genetic promoter element; genetically modified animals; glutathione transferase; histology; immunoprecipitation; in situ hybridization; laboratory mouse; northern blottings; osteoblasts; protein protein interaction; stem cells; transcription factor

DESCRIPTION (provided by applicant): This NICDR-K22 career development award application for Dr. Guang Zhou proposes a one-year Scholar Development Phase and a four-year Faculty Transition Phase. His Scholar Development Phase training will be performed at Baylor College of Medicine under the mentoring of Dr. Brendan Lee and Dr. Gerard Karsenty. During this period the proposed career development activities include Skeletal Dysplasia Clinical at Texas Children Hospital, special courses on craniofacial and dental genetics at UT-Dental Branch, mouse genetic seminar at M.D. Anderson Cancer Center, in situ hybridization and ES cell technique at Dr. Lee's laboratory, and bone histology training at Dr. Karsenty's laboratory. Dr. Zhou's immediate career goal is to complete his postdoctoral training and obtain an independent investigator position in an academic/medical center environment. For his long-term career Dr. Zhou will be committed to the biomedical research on bone and cartilage pathophysiology. Skeletogenesis involves the coordinated process of patterning, cell fate commitment, differentiation, growth, and remodeling. RUNX2/CBFA1 is a transcription factor essential for osteoblast differentiation, chondrocyte hypertrophy, and tooth formation. However little is known about the regulation of RUNX2 expression, especially during chondrogenesis. We recently identified SOX9, a transcription factor essential for cartilage formation including cranial neural crest cell differentiation, as a potent transcription repressor for RUNX2 transactivation. We propose to utilize both in vivo and in vitro tools to further understand the interaction between SOX9 and RUNX2 during skeletongenesis, especially chondrocyte hypertrophy. We will use in situ hybridization technique to study in parallel the expression patterns of Sox9 and Runx2 during chondrogenesis. GST-pulldown experiments will be performed to examine whether SOX9 physically interacts with RUNX2. In tissue culture systems, we will over-express SOX9 or its repression domain in chondrogenic cell line ATDC5 and pluripotent mesenchymal precursor cell line C2C12 to determine whether they can disrupt chondrocyte hypertrophy and osteogenesis in vitro. SOX9 effects on Runx2 expression and its downstream genes will be analyzed by Northern analysis and enzymatic assays. We will also generate transgenic mice mis-expressing SOX9 in hypertrophic chondrocytes to determine the consequences in vivo on long bone growth. This study will help us understand how proper skeletal patterning and cell fate commitment are achieved.

描述（由申请人提供）：广州博士的NICDR-K22职业发展奖申请包括为期一年的学者发展阶段和四年的教师过渡阶段。他的学者发展阶段培训将在贝勒医学院进行，由Brendan Lee博士和Gerard Karsenty博士指导。在此期间，提议的职业发展活动包括在德克萨斯儿童医院的骨骼发育不良临床，在ut -牙科分部的颅面和牙科遗传学的特殊课程，在md安德森癌症中心的小鼠遗传研讨会，在Lee博士实验室的原位杂交和胚胎干细胞技术，以及在Karsenty博士实验室的骨组织学培训。周博士的近期职业目标是完成他的博士后培训，并在学术/医疗中心环境中获得独立研究员的职位。周博士将长期致力于骨和软骨病理生理方面的生物医学研究。