REGULATION OF CRANIAL SUTURE MORPHOGENESIS

各种各样的先天性颅面畸形是由于 缝合形态发生过程中的缺陷，包括发育不全， 无法形成缝合;过早骨性结合;和骨发育不全。 更好地 了解，诊断和治疗这些疾病，这个项目的长期 目的是阐明控制缝合线形成的机制， 保持通畅，并作为骨生长中心发挥作用。 实现 这一目标提出了四个具体目标：1）表征 硬脑膜和骨膜与发育中颅骨的组织相互作用 （骨和缝线）对缝线形成、通畅性和生长至关重要 功能; 2）因素的表征和识别 由硬脑膜表达，这是缝合通畅所需的; 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 缝合周围组织的群体;以及4）测试 候选因子和拮抗剂对通畅性和生长功能的影响， 注射到冠状缝。 这些研究的模型是 发育中的大鼠冠状缝，将在 手术移植系统，在颅骨无血清培养中， 分离的细胞群和完整的新生动物。 的 缝合形态发生中每个相关组织的参与， 功能将通过在不同阶段移除组织来指示， 开发和评价缝线的形成， 通畅性和骨生长。 采用体外测量缝合线 狭窄，细胞增殖和成骨分化作为生物- 分析，涉及的因素将被分馏和识别。 肝素- 胎儿硬脑膜表达的结合因子的特征在于 深度，如果是新的，克隆和测序。 可溶性物质鉴别 细胞增殖和分化的影响因素 有助于阐明哪些成骨细胞 在缝合边缘产生骨并在缝合期间桥接缝合线， 骨结合 这些研究可以确定调节因素和信号传导 对缝线发育和功能至关重要的途径，当 会导致颅面病变

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.