Zebrafish Jaw Morphogenesis: Understanding Development Beyond the Embryo

描述（申请人提供）：斑马鱼已迅速成为早期颅面发育和模式研究的重要模型。在这个系统中的工作已经提供了重要的见解，无数的遗传信号，指导细胞活动和组织的相互作用，必要的咽骨架的适当组装。不幸的是，我们对胚胎期以后颅面发育的了解远远不够完整。在这里，我们提出利用实验可驯化的斑马鱼来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的颅面生长。本研究的目的是确定斑马鱼正常颅面生长和重塑的解剖变化特征，并评估遗传背景对这些过程的影响程度。接下来，我们将使用相同的统计方法来分析fgf缺乏情况下的颅面生长。Fgf是调节骨沉积和骨吸收的细胞间信号分子。我们将使用热休克诱导的转基因斑马鱼Fgf显性阴性受体系来破坏Fgf活性，并研究其对颅面生长和重塑的影响。最后，在与塔夫茨牙科医学院的Pamela C. Yelick合作进行的持续筛选中，将分析新发现的矿化组织斑马鱼突变体的胚胎后颅面发育。本研究的目的是识别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：本提案旨在通过结合实验胚胎学和统计形状分析来了解斑马鱼这一重要模型系统的胚胎后颅面发育。

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.