Significant progress has been made toward understanding the role of fgf8 in directing early embryonic patterning of the pharyngeal skeleton. Considerably less is known about the role this growth factor plays in the coordinated development, growth, and remodeling of the craniofacial skeleton beyond embryonic stages. To better understand the contributions of fgf8 in the formation of adult craniofacial architecture, we analyzed the skeletal anatomy of adult ace(ti282a)/fgf8 heterozygous zebrafish. Our results revealed distinct skeletal defects including facial asymmetries, aberrant craniofacial geometry, irregular patterns of cranial suturing, and ectopic bone formation. These defects are similar in presentation to several human craniofacial disorders (e.g., craniosynostosis, hemifacial microsomia), and may be related to increased levels of bone metabolism observed in ace(ti282a)/fgf8 heterozygotes. Moreover, skeletal defects observed in ace(ti282a)/fgf8 heterozygotes are consistent with expression patterns of fgf8 in the mature craniofacial skeleton. These data reveal previously unrecognized roles for fgf8 during skeletogenesis, and provide a basis for future investigations into the mechanisms that regulate craniofacial development beyond the embryo.
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