TY - JOUR
T1 - Morphological comparison of the craniofacial phenotypes of mouse models expressing the apert FGFR2 S252W mutation in neural crest- or mesoderm-derived tissues
AU - Heuzé, Yann
AU - Singh, Nandini
AU - Basilico, Claudio
AU - Jabs, Ethylin Wang
AU - Holmes, Greg
AU - Richtsmeier, Joan T.
N1 - Funding Information:
We are grateful to Dr. Christopher Percival for discussion on a previous version of this manuscript, and to Dr. Susan Motch, Tiffany Kim, and Hongseok Kim for managing the mice for imaging and the related image data. This work was supported by the National Institute of Dental and Craniofacial Research (Grant Numbers R01DE018500 and R01DE022988 ), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (Grant Number AR051358 ), and the National Institute of Child Health and Development ( R01HD038384 ).
PY - 2014/6
Y1 - 2014/6
N2 - Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part of a syndrome, such as Apert syndrome. Conditional expression of the Apert FGFR2 S252W mutation in cells derived from mesoderm was previously shown to be necessary and sufficient to cause coronal craniosynostosis. Here we used micro computed tomography images of mice expressing the Apert mutation constitutively in either mesoderm- or neural crest-derived cells to quantify craniofacial shape variation and suture fusion patterns, and to identify shape changes in craniofacial bones derived from the lineage not expressing the mutation, referred to here as secondary shape changes. Our results show that at postnatal day 0: (i) conditional expression of the FGFR2 S252W mutation in neural crest-derived tissues causes a more severe craniofacial phenotype than when expressed in mesoderm-derived tissues; and (ii) both mesoderm- and neural crest-specific mouse models display secondary shape changes. We also show that premature suture fusion is not necessarily dependent on the expression of the FGFR2 S252W mutation in the sutural mesenchyme. More specifically, it appears that suture fusion patterns in both mouse models are suture-specific resulting from a complex combination of the influence of primary abnormalities of biogenesis or signaling within the sutures, and timing.
AB - Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part of a syndrome, such as Apert syndrome. Conditional expression of the Apert FGFR2 S252W mutation in cells derived from mesoderm was previously shown to be necessary and sufficient to cause coronal craniosynostosis. Here we used micro computed tomography images of mice expressing the Apert mutation constitutively in either mesoderm- or neural crest-derived cells to quantify craniofacial shape variation and suture fusion patterns, and to identify shape changes in craniofacial bones derived from the lineage not expressing the mutation, referred to here as secondary shape changes. Our results show that at postnatal day 0: (i) conditional expression of the FGFR2 S252W mutation in neural crest-derived tissues causes a more severe craniofacial phenotype than when expressed in mesoderm-derived tissues; and (ii) both mesoderm- and neural crest-specific mouse models display secondary shape changes. We also show that premature suture fusion is not necessarily dependent on the expression of the FGFR2 S252W mutation in the sutural mesenchyme. More specifically, it appears that suture fusion patterns in both mouse models are suture-specific resulting from a complex combination of the influence of primary abnormalities of biogenesis or signaling within the sutures, and timing.
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U2 - 10.1016/j.bone.2014.03.003
DO - 10.1016/j.bone.2014.03.003
M3 - Article
C2 - 24632501
AN - SCOPUS:84896971754
SN - 8756-3282
VL - 63
SP - 101
EP - 109
JO - Bone
JF - Bone
ER -