The role of Twisted Gastrulation in Mouse Development

扭曲原肠胚形成在小鼠发育中的作用

• 批准号: 6696589
• 负责人: Anna Petryk
• 金额: $ 10.8万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-15 至 2006-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6696589
• 关键词: role; Twisted; Gastrulation; Mouse; Development

DESCRIPTION (provided by applicant): Dr. Petryk is a pediatric endocrinologist at the University of Minnesota. The candidate's long-term goal is to pursue an academic career devoted primarily to basic research. As a pediatric resident and an endocrinology fellow, Dr. Petryk was involved in the care of a significant number of patients with congenital malformations and growth disorders. Her interest in the molecular basis of these health problems led her to pursue research training in developmental biology in order to gain understanding of their pathogenesis as a basis for possible therapeutic interventions in the future. Dr. Petryk has generated twisted gastrulation (tsg) deficient mice that will serve as a model to study molecular and cellular mechanisms of skeletal and neural tube development. This work will be carried out under the mentorship of Dr. Michael O'Connor. Dr. Petryk has also established key collaborations that will be instrumental in her career development plan. Tsg has recently been recognized as a new bone morphogenetic protein (BMP) antagonist that is required for normal embryonic development of invertebrate and lower vertebrate species. Tsg is thought to act synergistically with another extracellular protein Chordin (Chd) to inhibit BMP2 and BMP4 signaling by preventing their binding to the receptors. The role of Tsg in mammalian development is currently unknown. Preliminary phenotypic analysis indicates that Tsg-deficient mice have reduced growth and skeletal defects similar to those that occur in spina bifida. Chd-deficient mice also have skeletal defects and abnormal neural tube patterning. The comparison of the phenotypes of mice deficient in Chd versus those deficient in Tsg, and generation of Tsg;Chd double mutants, will offer new insight into the molecular mechanisms of congenital malformations. The candidate will pursue the following specific aims: 1) Characterize the mechanisms underlying the skeletal defects and growth deficiency in Tsg-deficient mice; 2) Understand the interactions between Tsg and Chd in mouse embryonic development by generating and characterizing Tsg;Chd double mutants.

描述（由申请人提供）：Dr. Petryk是明尼苏达大学的儿科内分泌学家。候选人的长期目标是从事主要致力于基础研究的学术生涯。作为儿科住院医师和内分泌学研究员，佩特里克博士参与了大量先天性畸形和生长障碍患者的护理。她对这些健康问题的分子基础的兴趣促使她继续进行发育生物学的研究培训，以便了解其发病机制，为将来可能的治疗干预奠定基础。Petryk博士培育出扭曲原肠胚（tsg）缺陷小鼠，将作为研究骨骼和神经管发育的分子和细胞机制的模型。这项工作将在Michael O’connor博士的指导下进行。Petryk博士还建立了重要的合作关系，这将有助于她的职业发展计划。