REGULATION OF CRANIAL SUTURE MORPHOGENESIS

颅缝形态发生的调节

• 批准号: 2131295
• 负责人: Roy Clinton Ogle
• 金额: $ 13.46万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1997-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2131295
• 关键词: bioassay; bone development; cell cycle; cell differentiation; cell free system; cell growth regulation; cellular pathology; craniofacial dysostosis; craniosynostosis; deficient growth media; developmental neurobiology; dura mater; fibroblast growth factor; histogenesis; immunocytochemistry; in situ hybridization; laboratory rat; mesenchyme; molecular pathology; nucleic acid sequence; osteogenesis; periosteums; polymerase chain reaction; skull; tissue /cell culture

A variety of congenital craniofacial anomalies arise as a consequence of defects in the process of suture morphogenesis, including agenesis, the failure to form sutures; premature synostosis; and dysostosis. To better understand, diagnose and treat these disorders, this project's long-term goal is elucidating the mechanisms governing suture formation, maintenance of patency, and function as a bone growth center. To achieve this goal four specific aims are proposed: 1) characterization of the tissue interactions of dura mater and periosteum with developing calvaria (bones and suture) critical to suture formation, patency and growth function; 2) characterization and identification of the factor(s) expressed by dura mater which are required for suture patency; 3) characterization of the local-acting factors and interacting molecules regulating proliferation and differentiation in the osteogenic cell populations of the peri-sutural tissues; and 4) test the effects of candidate factors and antagonists on patency and growth functions by injection into coronal sutures. The model for these studies is the developing coronal suture of the rat, which will be examined in a surgical transplant system, in serum free culture of calvaria, in isolated cell populations and in intact neonatal animals. The involvement of each associated tissue in the suture morphogenesis and function will be indicated by removing the tissue at various stages of development and evaluating the formation of sutures, maintenance of patency and bone growth. Employing in vitro measurement of sutural stenosis, cellular proliferation and osteogenic differentiation as bio- assays, factors involved will be fractionated and identified. A heparin- binding factor expressed by fetal dura mater will be characterized in depth, and if novel, cloned and sequenced. Identification of soluble factors influencing proliferation and differentiation of and expressed by each cell population will help elucidate which osteogenic cells produce the bone at the sutural margin and bridge the suture during synostosis. These studies may identify regulatory factors and signalling pathways critical to suture development and function, which when perturbed contribute to craniofacial pathology.

由于出现了各种先天性颅面异常 在缝合形态发生过程中的缺陷，包括发育不全， 未能形成缝合线；早产平均症状；和炎症性障碍。 更好 了解，诊断和治疗这些疾病，该项目的长期 目标是阐明有关缝合形成的机制， 维持通畅性并充当骨骼生长中心。 实现 该目标提出了四个具体目标：1）表征 硬脑膜和骨膜与发育中的钙的组织相互作用 （骨骼和缝合线）对于缝合形成，通畅和生长至关重要 功能; 2）表征和识别因子 由缝合通畅所需的硬脑膜表达； 3） 局部作用因子和相互作用分子的表征 调节成骨细胞的增殖和分化 核周围组织的种群； 4）测试 候选因素和拮抗剂对通畅和增长功能 注入冠状缝合线。 这些研究的模型是 开发大鼠的冠状缝合线，将在 手术移植系统，在瓦尔瓦里亚的无血清培养物中 孤立的细胞种群和完整的新生动物。 这 每个相关组织参与缝合形态发生和 功能将通过在各个阶段删除组织来指示 开发和评估缝合线的形成，维护 通畅和骨骼生长。 使用缝合的体外测量 狭窄，细胞增殖和成骨分化为生物 测定，涉及的因素将被分离和识别。 肝素 - 用胎儿硬脑膜表达的结合因子将在 深度，如果是新颖的，则是克隆和测序的。 可溶性的识别 影响和表达的增殖和分化的因素 每个细胞种群将有助于阐明哪个成骨细胞 在缝合边缘产生骨头，并在 平音。 这些研究可能确定调节因素和信号传导 对于缝合的开发和功能至关重要的途径，当 扰动有助于颅面病理学。