DEVELOPMENT OF THE PALATE AND CRANIOFACIAL MESENCHYME

腭和颅面间充质的发育

• 批准号: 6176631
• 负责人: ELIZABETH D HAY
• 金额: $ 24.57万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176631
• 关键词: antibody; cell cell interaction; cell transformation; chick embryo; cleft palate; connective tissue development; craniofacial; developmental genetics; electroporation; embryo /fetus tissue /cell culture; embryogenesis; epithelium; histogenesis; integrins; intercellular connection; laboratory mouse; mesenchyme; palate; transforming growth factors

DESCRIPTION (adapted from the Investigator's abstract): The broad objective of this application is to understand the tissue transitions involved in the development of the palate and craniofacial mesenchyme. Transformation of the medial edge epithelia (MEE) to mesenchyme in the paired palatal shelves from avian and rodent models will be examined. This represents a model for embryonic tissue remodeling and has potential importance to better understand failure of the palatal shelves to fuse in humans. The Principal Investigator's laboratory was the first to propose and demonstrate that the MEE undergoes epithelial-mesenchymal transformation (EMT) after fusing to form a midline seam, and that the resulting mesenchymal cells become part of the palate connective tissue, thus establishing confluence of the palatal stroma. It is likely that EMT is involved in other craniofacial processes where epithelial fuse, consequently studies are proposed to examine the formation of the upper lip. Understanding the cellular mechanism of palatal EMT will result in new approaches to defining the causes of congenital facial anomalies, such as cleft palate and other facial clefts that may result from failure of the EMT process. The specific aims are to study (1) the role of cell-cell contacts between opposing palatal shelves in initiation of EMT in the MEE; (2) the role of cell-matrix interactions and TGF-beta3 in the emigration phase of EMT; and (3) the role of defective EMT in cleft palate and in cleft lip. It is expected that beta-catenin and plakoglobin associated with the newly formed MEE junctions are the signaling molecules involved in initiating palatal EMT. Also it is expected that matrix-stimulated tyrosine kinases interact with growth factors at the plasmalemma level to promote emigration. Knowledge of the basic cell biology will lead to more effective treatment of human facial clefting.

描述（根据研究者的摘要进行了改编）：该应用的广泛目的是了解触时和颅面间质发展中涉及的组织过渡。将检查将内侧边缘上皮（MEE）转化为来自鸟类和啮齿动物模型的配对pa架架子中的间质。这代表了胚胎组织重塑的模型，并且潜在的重要性是更好地了解palatal架子在人类中融合的失败。首席研究者的实验室是第一个提出并证明MEE融合后经历上皮间质转化（EMT）以形成中线接缝，并且所得的间充质细胞成为pa骨结缔组织的一部分，从而建立了palatal骨膜的融合。 EMT可能参与了其他颅面过程，在这些过程中，提出了上皮融合的研究，因此提出了研究上唇的形成。了解pa骨EMT的细胞机制将导致定义先天性面部异常原因的新方法，例如left裂和其他因EMT过程失败而导致的面部裂缝。具体的目的是研究（1）相反的pa架架子在MEE中启动EMT之间的细胞细胞接触的作用； （2）细胞 - 矩阵相互作用和TGF-BETA3在EMT的移民阶段的作用； （3）EMT有缺陷在left裂和唇裂中的作用。预计与新形成的MEE连接相关的β-catenin和plakoglobin是启动palatal EMT的信号分子。还可以预期，基质刺激的酪氨酸激酶与浆膜水平上的生长因子相互作用以促进移民。对基本细胞生物学的了解将导致对人面部裂fe的更有效治疗。