Zebrafish Jaw Morphogenesis: Understanding Development Beyond the Embryo

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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.