Zebrafish Jaw Morphogenesis: Understanding Development Beyond the Embryo

斑马鱼颌形态发生：了解胚胎以外的发育

• 批准号: 7646070
• 负责人: Craig Albertson
• 金额: $ 21.9万
• 依托单位: SYRACUSE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7646070
• 关键词: Address; Adult; Affect; Biological Models; Bone Development; Boston; Collaborations; Complex; Data; Defect; Dental Schools; Deposition; Development; Disease; Embryo; Embryology; Exhibits; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Foundations; Future; Genetic; Goals; Growth; Growth and Development function; Health; Heat-Shock Response; Human; Investigation; Jaw; Literature; Maintenance; Medicine; Methods; Molecular; Morphogenesis; Pattern; Phenotype; Process; Regulation; Role; Sampling; Shapes; Siblings; Signal Pathway; Signal Transduction; Signaling Molecule; Signaling Pathway Gene; Skeletal Development; Skeleton; Staging; Staining method; Stains; Statistical Methods; Study models; System; Time; Tissues; Transgenic Organisms; Work; Zebrafish; base; bone; craniofacial; craniofacial complex; gene function; human disease; insight; malformation; mutant; novel; public health relevance; regional difference; research study; skeletal; trait

DESCRIPTION (provided by applicant): The zebrafish has quickly emerged as an important model for the study of early craniofacial developmental and patterning. Work in this system has provided significant insights into the myriad genetic signals that direct the cellular activities and tissue interactions necessary for proper assembly of the pharyngeal skeleton. Unfortunately our understanding of craniofacial development beyond embryonic stages is far less complete. Here we propose to exploit the experimentally tractable zebrafish to investigate post-embryonic craniofacial development, growth, and remodeling. Three specific aims are proposed. First, we will characterize craniofacial growth in two wild-type zebrafish stains using sophisticated quantitative shape analyses. The goal of this aim is to define the anatomical shifts that characterize normal craniofacial growth and remodeling in zebrafish, and to assess the degree to which genetic background influences these processes. Next, we will use the same statistical methods to analyze craniofacial growth in the context of Fgf-deficiency. Fgf's are intercellular signaling molecules that regulate bone deposition and resorption. We will use a heat-shock inducible dominent- negative Fgf receptor line of transgenic zebrafish to disrupt Fgf activity and examine the effects on craniofacial growth and remodeling. Finally, post-embryonic craniofacial development will be analyzed in newly identified mineralized tissue zebrafish mutants in an ongoing screen being performed in collaboration with Pamela C. Yelick at Tufts School of Dental Medicine. The goal of this aim is to identify and characterize novel mutants that exhibit stage-specific defects in skeletal growth and remodeling, and to begin to elucidate the signaling pathways that regulate these processes. These data will make novel contributions to our understanding of the coordinated processes of craniofacial development, growth and remodeling. PUBLIC HEALTH RELEVANCE: This proposal seeks to understand post-embryonic craniofacial development in an important model system - the zebrafish - by combining experimental embryology with statistical shape analyses.

描述（由申请人提供）：斑马鱼已迅速成为研究早期颅面发育和模式的重要模型。在这个系统中的工作提供了大量的遗传信号，指导细胞活动和组织的相互作用，必要的正确组装咽骨骼的显着见解。不幸的是，我们对胚胎期以后颅面发育的了解远没有那么完整。在这里，我们建议利用实验上听话的斑马鱼研究胚胎后颅面发育，生长和重塑。提出了三个具体目标。首先，我们将使用复杂的定量形状分析来表征两种野生型斑马鱼染色剂的颅面生长。这个目标的目的是定义的解剖结构的变化，特征正常颅面生长和重塑斑马鱼，并评估遗传背景影响这些过程的程度。接下来，我们将使用相同的统计方法来分析在FGF缺乏的背景下颅面生长。成纤维细胞生长因子是调节骨沉积和吸收的细胞间信号分子。我们将使用热休克诱导的显性阴性Fgf受体系的转基因斑马鱼来破坏Fgf活性，并检查对颅面生长和重塑的影响。最后，胚胎后颅面发育将在新鉴定的矿化组织斑马鱼突变体中进行分析，该突变体正在与Pamela C.塔夫茨牙科医学院的Yelick。本研究的目的是鉴定和表征在骨骼生长和重塑中表现出阶段特异性缺陷的新型突变体，并开始阐明调节这些过程的信号通路。这些数据将为我们理解颅面发育、生长和重塑的协调过程做出新的贡献。公共卫生相关性：这项建议旨在了解胚胎后颅面发育的一个重要的模型系统-斑马鱼-结合实验胚胎学与统计形状分析。