The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis

颌关节形态发生的分子遗传学和细胞生物学

• 批准号: 7546014
• 负责人: James Tucker Nichols
• 金额: $ 4.72万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7546014
• 关键词: Address; Adhesions; Adopted; Animals; Biological; Biological Models; Biology; Branchial arch structure; Cancer Etiology; Cartilage; Cell Communication; Cell Differentiation process; Cell Separation; Cell physiology; Cells; Cellular biology; Cephalic; Chondrocytes; Complex; Connective Tissue; Development; Disease; Dorsal; Dose; Ectopic Expression; Elements; Ensure; Eph Family Receptors; Ephrins; Event; First Pharyngeal Arch; Fluorescent in Situ Hybridization; Fostering; Gene Expression; Genes; Genetic; Genetic Screening; Human; Joints; Knowledge; Label; Larva; Ligands; Malignant Neoplasms; Maps; Mediating; Mediator of activation protein; Mesenchymal; Modeling; Molecular; Molecular Genetics; Monitor; Morphogenesis; Mutation; Neural Crest Cell; Peptide Signal Sequences; Phenotype; Process; Public Health; Role; Signal Transduction; Signaling Molecule; Site; Skeleton; Specific qualifier value; Stem cells; Structure; System; Temporomandibular Joint; Testing; Therapeutic; Tissues; To specify; Work; Zebrafish; base; bone; cell motility; cell type; craniofacial; gene discovery; gene function; human disease; intercellular communication; interest; loss of function; migration; mutant; precursor cell; prevent; programs; receptor; research study; segregation; skeletal; stem; tool

DESCRIPTION (provided by applicant): Joints are complex anatomical structures that facilitate the articulation of skeletal elements. Jaw joints of larval zebrafish provide a simplified model system for understanding the molecular genetics and cell biology of joint formation, where signaling molecules instruct stem-like cells to form the cartilages and joints that constitute the young zebrafish skeleton. I will examine a gene that I hypothesize prevents cartilage formation in the joint region. In addition, I propose to examine the molecular "rules" that govern cell movement, adhesion, and repulsion to ensure cells reside at their proper anatomical site. Furthermore, I will discover new genes that are required for zebrafish jaw joint formation. These studies will aid in our understanding of human joint development and disorders. Zebrafish larvae are the optimal system for these studies as they are optically transparent, and develop externally. Therefore, all of the cellular processes I propose to study can be witnessed in the developing animal. I will monitor where and when the genes I am interested in are turned on, and will reduce and increase their function using previously validated tools. Perturbation of normal function will foster discovery of the respective roles for genes during jaw joint formation. Relevance to public health: These studies investigate the normal function of signaling molecules that are implicated in cancer. A working knowledge of how cancer-causing genes function normally is paramount to understanding their role in human disease. Furthermore, my studies will aid in understanding how signaling molecules control the development of a wide array of cell types from a single stem-like precursor cell. This knowledge is of tremendous value for stem cell therapeutics.

描述（由申请人提供）：关节是复杂的解剖结构，可促进骨骼元素的表达。幼虫斑马鱼的下颌关节提供了一个简化的模型系统，用于理解关节形成的分子遗传学和细胞生物学，其中信号分子指示茎样细胞形成构成年轻斑马鱼骨骼的软骨和关节。我将检查一个我假设的基因，可以防止关节区域的软骨形成。此外，我建议检查控制细胞运动，粘附和排斥的分子“规则”，以确保细胞居住在其适当的解剖部位。此外，我将发现斑马鱼颌关节形成所需的新基因。这些研究将有助于我们理解人类联合发展和疾病。斑马鱼幼虫是这些研究的最佳系统，因为它们在光学上是透明的，并在外部发展。因此，我建议研究的所有细胞过程都可以在发展中的动物中见证。我将监视我感兴趣的基因的何时何地打开，并使用先前验证的工具降低和提高其功能。正常功能的扰动将促进下颌关节形成过程中基因的各个作用。与公共卫生的相关性：这些研究研究了与癌症有关的信号分子的正常功能。关于致癌基因功能的工作知识通常对于了解其在人类疾病中的作用至关重要。此外，我的研究将有助于了解信号分子如何从单个茎样前体细胞中控制各种细胞类型的发展。这种知识对于干细胞疗法具有巨大的价值。