The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis

描述(申请人提供)：关节是复杂的解剖结构，便于骨骼元素的连接。斑马鱼幼体的颌骨关节为理解关节形成的分子遗传学和细胞生物学提供了一个简化的模型系统，其中信号分子指示干细胞样细胞形成软骨和关节，构成幼年斑马鱼的骨骼。我将研究一种基因，我假设它可以防止关节区域的软骨形成。此外，我建议研究控制细胞运动、黏附和排斥的分子“规则”，以确保细胞驻留在其适当的解剖位置。此外，我将发现斑马鱼下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的联合发育和疾病。斑马鱼幼体是这些研究的最佳系统，因为它们是光学透明的，并在外部发育。因此，我打算研究的所有细胞过程都可以在发育中的动物身上看到。我将监测我感兴趣的基因何时何地被激活，并将使用以前经过验证的工具来减少和增加它们的功能。对正常功能的干扰将促进发现在颌骨关节形成过程中基因各自的作用。与公共健康相关：这些研究调查了与癌症有关的信号分子的正常功能。对致癌基因如何正常发挥作用的实用知识对于了解它们在人类疾病中的作用至关重要。此外，我的研究将有助于理解信号分子如何控制单个干细胞样前体细胞发育成多种细胞类型。这一知识对干细胞疗法具有巨大的价值。

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.