Midface and upper airway dysgenesis in FGFR2-related craniosynostosis involves multiple tissue-specific and cell cycle effects

Greg Holmes, Courtney O’Rourke, Susan Marie Perrine, Na Lu, Harm van Bakel, Joan Therese Richtsmeier, Ethylin Wang Jabs

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Midface dysgenesis is a feature of more than 200 genetic conditions in which upper airway anomalies frequently cause respiratory distress, but its etiology is poorly understood. Mouse models of Apert and Crouzon craniosynostosis syndromes exhibit midface dysgenesis similar to the human conditions. They carry activating mutations of Fgfr2, which is expressed in multiple craniofacial tissues during development. Magnetic resonance microscopy of three mouse models of Apert and Crouzon syndromes revealed decreased nasal passage volume in all models at birth. Histological analysis suggested overgrowth of the nasal cartilage in the two Apert syndrome mouse models. We used tissue-specific gene expression and transcriptome analysis to further dissect the structural, cellular and molecular alterations underlying midface and upper airway dysgenesis in Apert Fgfr2+/S252W mutants. Cartilage thickened progressively during embryogenesis because of increased chondrocyte proliferation in the presence of Fgf2. Oral epithelium expression of mutant Fgfr2, which resulted in a distinctive nasal septal fusion defect, and premature facial suture fusion contributed to the overall dysmorphology. Midface dysgenesis in Fgfr2-related craniosynostosis is a complex phenotype arising from the combined effects of aberrant signaling in multiple craniofacial tissues.

Original languageEnglish (US)
Article numberdev166488
JournalDevelopment (Cambridge)
Volume145
Issue number19
DOIs
StatePublished - Oct 1 2018

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Craniosynostoses
Craniofacial Dysostosis
Acrocephalosyndactylia
Cell Cycle
Nose
Nasal Cartilages
Gene Expression Profiling
Chondrocytes
Sutures
Cartilage
Embryonic Development
Microscopy
Magnetic Resonance Spectroscopy
Epithelium
Parturition
Phenotype
Gene Expression
Mutation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

Cite this

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title = "Midface and upper airway dysgenesis in FGFR2-related craniosynostosis involves multiple tissue-specific and cell cycle effects",
abstract = "Midface dysgenesis is a feature of more than 200 genetic conditions in which upper airway anomalies frequently cause respiratory distress, but its etiology is poorly understood. Mouse models of Apert and Crouzon craniosynostosis syndromes exhibit midface dysgenesis similar to the human conditions. They carry activating mutations of Fgfr2, which is expressed in multiple craniofacial tissues during development. Magnetic resonance microscopy of three mouse models of Apert and Crouzon syndromes revealed decreased nasal passage volume in all models at birth. Histological analysis suggested overgrowth of the nasal cartilage in the two Apert syndrome mouse models. We used tissue-specific gene expression and transcriptome analysis to further dissect the structural, cellular and molecular alterations underlying midface and upper airway dysgenesis in Apert Fgfr2+/S252W mutants. Cartilage thickened progressively during embryogenesis because of increased chondrocyte proliferation in the presence of Fgf2. Oral epithelium expression of mutant Fgfr2, which resulted in a distinctive nasal septal fusion defect, and premature facial suture fusion contributed to the overall dysmorphology. Midface dysgenesis in Fgfr2-related craniosynostosis is a complex phenotype arising from the combined effects of aberrant signaling in multiple craniofacial tissues.",
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Midface and upper airway dysgenesis in FGFR2-related craniosynostosis involves multiple tissue-specific and cell cycle effects. / Holmes, Greg; O’Rourke, Courtney; Perrine, Susan Marie; Lu, Na; van Bakel, Harm; Richtsmeier, Joan Therese; Jabs, Ethylin Wang.

In: Development (Cambridge), Vol. 145, No. 19, dev166488, 01.10.2018.

Research output: Contribution to journalArticle

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