Nathaniel Zbasnik1, Katie Dolan1, Stephanie A Buczkowski2, Rebecca M Green3, Benedikt Hallgrímsson4, Ralph S Marcucio5, Anne M Moon2,6, Jennifer L Fish1. 1. Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA. 2. Department of Molecular and Functional Genomics, Geisinger Medical Center, Danville, Pennsylvania, USA. 3. Center for Craniofacial and Dental Genetics and Department of Oral and Craniofacial Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 4. Department of Cell Biology and Anatomy, Alberta Chidren's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada. 5. Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco, San Francisco, California, USA. 6. Departments of Pediatrics and Human Genetics, University of Utah, Salt Lake City, Utah, USA.
Abstract
BACKGROUND: Asymmetries in craniofacial anomalies are commonly observed. In the facial skeleton, the left side is more commonly and/or severely affected than the right. Such asymmetries complicate treatment options. Mechanisms underlying variation in disease severity between individuals as well as within individuals (asymmetries) are still relatively unknown. RESULTS: Developmental reductions in fibroblast growth factor 8 (Fgf8) have a dosage dependent effect on jaw size, shape, and symmetry. Further, Fgf8 mutants have directionally asymmetric jaws with the left side being more affected than the right. Defects in lower jaw development begin with disruption to Meckel's cartilage, which is discontinuous. All skeletal elements associated with the proximal condensation are dysmorphic, exemplified by a malformed and misoriented malleus. At later stages, Fgf8 mutants exhibit syngnathia, which falls into two broad categories: bony fusion of the maxillary and mandibular alveolar ridges and zygomatico-mandibular fusion. All of these morphological defects exhibit both inter- and intra-specimen variation. CONCLUSIONS: We hypothesize that these asymmetries are linked to heart development resulting in higher levels of Fgf8 on the right side of the face, which may buffer the right side to developmental perturbations. This mouse model may facilitate future investigations of mechanisms underlying human syngnathia and facial asymmetry.
BACKGROUND: Asymmetries in craniofacial anomalies are commonly observed. In the facial skeleton, the left side is more commonly and/or severely affected than the right. Such asymmetries complicate treatment options. Mechanisms underlying variation in disease severity between individuals as well as within individuals (asymmetries) are still relatively unknown. RESULTS: Developmental reductions in fibroblast growth factor 8 (Fgf8) have a dosage dependent effect on jaw size, shape, and symmetry. Further, Fgf8 mutants have directionally asymmetric jaws with the left side being more affected than the right. Defects in lower jaw development begin with disruption to Meckel's cartilage, which is discontinuous. All skeletal elements associated with the proximal condensation are dysmorphic, exemplified by a malformed and misoriented malleus. At later stages, Fgf8 mutants exhibit syngnathia, which falls into two broad categories: bony fusion of the maxillary and mandibular alveolar ridges and zygomatico-mandibular fusion. All of these morphological defects exhibit both inter- and intra-specimen variation. CONCLUSIONS: We hypothesize that these asymmetries are linked to heart development resulting in higher levels of Fgf8 on the right side of the face, which may buffer the right side to developmental perturbations. This mouse model may facilitate future investigations of mechanisms underlying human syngnathia and facial asymmetry.
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Authors: Nathan M Young; H Jonathan Chong; Diane Hu; Benedikt Hallgrímsson; Ralph S Marcucio Journal: Development Date: 2010-09-08 Impact factor: 6.868
Authors: Rebecca M Green; Jennifer L Fish; Nathan M Young; Francis J Smith; Benjamin Roberts; Katie Dolan; Irene Choi; Courtney L Leach; Paul Gordon; James M Cheverud; Charles C Roseman; Trevor J Williams; Ralph S Marcucio; Benedikt Hallgrímsson Journal: Nat Commun Date: 2017-12-06 Impact factor: 14.919