Postnatal brain and skull growth in an Apert syndrome mouse model

Authors

  • Cheryl A. Hill,

    1. Department of Pathology and Anatomical Sciences, University of Missouri-School of Medicine, Columbia, Missouri
    2. Department of Basic Medical Sciences, University of Arizona College of Medicine Phoenix, Phoenix, Arizona
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  • Neus Martínez-Abadías,

    1. Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania
    2. EMBL-CRG Systems Biology Research Unit, Center for Genomic Regulation, Universitat Pompeu Fabra, Barcelona, Spain
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  • Susan M. Motch,

    1. Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania
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  • Jordan R. Austin,

    1. Department of Pathology and Anatomical Sciences, University of Missouri-School of Medicine, Columbia, Missouri
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  • Yingli Wang,

    1. Department of Genetics and Genomic Sciences, Mt. Sinai School of Medicine, New York, New York
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  • Ethylin Wang Jabs,

    1. Department of Genetics and Genomic Sciences, Mt. Sinai School of Medicine, New York, New York
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  • Joan T. Richtsmeier,

    1. Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania
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  • Kristina Aldridge

    Corresponding author
    1. Department of Pathology and Anatomical Sciences, University of Missouri-School of Medicine, Columbia, Missouri
    • Department of Pathology and Anatomical Sciences, University of Missouri School of Medicine, One Hospital Drive, M309 Med Sci Bldg, Columbia, MO 65212.
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  • How to Cite this Article: Hill CA, Martínez-Abadías N, Motch SM, Austin JR, Wang Y, Jabs EW, Richtsmeier JT, Aldridge K. 2013. Postnatal brain and skull growth in an Apert syndrome mouse model. Am J Med Genet Part A 161A:745–757

Abstract

Craniofacial and neural tissues develop in concert throughout prenatal and postnatal growth. FGFR-related craniosynostosis syndromes, such as Apert syndrome (AS), are associated with specific phenotypes involving both the skull and the brain. We analyzed the effects of the FGFR P253R mutation for AS using the Fgfr2+/P253R Apert syndrome mouse to evaluate the effects of this mutation on these two tissues over the course of development from day of birth (P0) to postnatal day 2 (P2). Three-dimensional magnetic resonance microscopy and computed tomography images were acquired from Fgfr2+/P253R mice and unaffected littermates at P0 (N = 28) and P2 (N = 20).Three-dimensional coordinate data for 23 skull and 15 brain landmarks were statistically compared between groups. Results demonstrate that the Fgfr2+/P253R mice show reduced growth in the facial skeleton and the cerebrum, while the height and width of the neurocranium and caudal regions of the brain show increased growth relative to unaffected littermates. This localized correspondence of differential growth patterns in skull and brain point to their continued interaction through development and suggest that both tissues display divergent postnatal growth patterns relative to unaffected littermates. However, the change in the skull–brain relationship from P0 to P2 implies that each tissue affected by the mutation retains a degree of independence, rather than one tissue directing the development of the other. © 2013 Wiley Periodicals, Inc.

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